Role of macrophages in disease development and progression
|
|
|
- Victor Pearson
- 6 years ago
- Views:
Transcription
1 Role of macrophages in disease development and progression Frank Tacke 3rd Paris NASH Symposium July 6, 2017 Dept. of Medicine III Gastroenterology, Metabolic Diseases and Intensive Care Medicine
2 Disclosures Frank Tacke Research support (materials, funding): Tobira/Allergan (CVC), Noxxon (mnox-e36), Galapagos Speaker/Advisory Board: Tobira/Allergan, Gilead, AbbVie, BMS, Boehringer, Galapagos, Intercept, Falk, Inventiva
3 F4/80 fibrosis H&E Macrophage accumulation is a hallmark of progressive non-alcoholic steatohepatitis CD11b control NASH model 4% 33% 4% 4% F4/80 Baeck C / Tacke F. Hepatology 2014 Ehling J / Tacke F. Gut 2014 Wehr A / Tacke F. J Immunol 2013 Baeck C / Tacke F. Gut 2012 Karlmark KR / Tacke F. Hepatology 2009 Tacke F / Randolph GJ. J Clin Invest 2007
4 Monocyte / macrophage heterogeneity in liver inflammation, fibrosis and cancer Origin homeostasis vs. inflammation Mass E / Geissmann F. Science Bleriot C, et al. Immunity 2015 Scott CL / Guilliams M. Nat Commun 2016 Wang J, Kubes P. Cell monocytes Ly6C hi macrophages CCR2 Ly6C lo selected examples for recent research Kupffer cells Differentiation microenvironmental signals shape phenotype M1 polarization M2 polarization inflammation tumor inflammation remodelling tumor Function regarding liver injury pro-inflammatory (can) develop into restorative macrophages Xue J / Schultze J. Immunity 2014 Beattie J / Kane PM. J Hepatol 2016 Bartneck M / Tacke F. Hepatology 2016 Dal-Secco D / Kubes P. J Exp Med Ramachandran P / Iredale JP. PNAS 2012 Baeck C / Tacke F. Hepatology 2014
5 Monocytes and macrophages in liver diseases Acute liver injury NASH and fibrosis Immunometabolism
6 Cell Death triggers immune cell homing: acetaminophen injury Acetaminophen (APAP) 7mg/ml on primary mouse hepatocytes
7 Role of infiltrating monocytes: acetaminophen induced acute liver injury Krenkel O, Mossanen JC, Tacke F. Hepatobiliary Surg Nutr. 2014; 3(6): based on: Huebener / Schwabe RF. J Clin Invest 2015; You Q / Ju C. Biochem Pharmacol. 2013; Zigmond E / Varol C. J Immunol 2014
8 Role of infiltrating monocytes: acetaminophen induced acute liver injury Krenkel O, Mossanen JC, Tacke F. Hepatobiliary Surg Nutr. 2014; 3(6): based on: Huebener / Schwabe RF. J Clin Invest 2015; You Q / Ju C. Biochem Pharmacol. 2013; Zigmond E / Varol C. J Immunol 2014
9 Monocyte and macrophage populations in experimental liver injury intravital multiphoton-microscopy Heymann F / Tacke F. Hepatology 2015 Heymann F / Tacke F. J Vis Exp 2015 Analyses of migration and cell-cellinteractions in real-time in vivo
10 CCR2 + inflammatory monocyte recruitment after acetaminophen overdose control CCR2-eGFP (reporter) Latex particles SHG (collagen) APAP 9 hours progressive accumulation of CCR2 + monocytes at 9-12h after APAP injury Mossanen JC, Krenkel O / Tacke F. Hepatology 2016; 64(5):
11 CCR2 + inflammatory monocyte recruitment after acetaminophen overdose control CCR2-eGFP (reporter) Latex particles SHG (collagen) APAP 9 hours progressive accumulation of CCR2 + monocytes at 9-12h after APAP injury Mossanen JC, Krenkel O / Tacke F. Hepatology 2016; 64(5):
12 Ccr2 -/- mice are protected in the early phase of acetaminophen induced liver injury CD11b WT 5.41 % 0 h APAP % 12 h APAP WT Ccr2 -/- n % 6.30 % Ccr2 -/ % 2.32 % F4/ % WT Ccr2 -/- n % Monocyte-derived Macrophages (MoMF) Kupffer Cells (KC) Mossanen JC, Krenkel O / Tacke F. Hepatology 2016; 64(5):
13 CCR2 + monocyte-derived macrophages have an inflammatory phenotype FACS sorting Nanostring analysis for 561 gene targets associated with inflammation Mossanen JC, Krenkel O / Tacke F. Hepatology 2016; 64(5):
14 Inflammatory CCR2 + macrophages in human acetaminophen acute liver failure Mossanen JC, Krenkel O / Tacke F. Hepatology 2016; 64(5): similar data by Antoniades CG / Wendon J. Hepatology 2012; 56(2):735-46
15 Monocytes and macrophages in liver diseases Acute liver injury NASH and fibrosis Immunometabolism
16 Monocyte / macrophage subsets during regression of liver fibrosis liver inflammatory Ly6C high monocyte fibrogenic Ly6C+ macrophage adipose tissue PDGF, TGFb, TNF, IL-1b hepatocytes Hepatic stellate cell (HSC) activated HSC (myofibroblast) Extracellular matrix (ECM) Krenkel O & Tacke F. Nat Rev Immunol 2017
17 Monocyte / macrophage subsets during regression of liver fibrosis liver inflammatory Ly6C high monocyte fibrogenic Ly6C+ macrophage adipose tissue Cenicriviroc (CVC): orally available dual CCR2/CCR5 inhibitor PDGF, TGFb, TNF, IL-1b hepatocytes Hepatic stellate cell (HSC) activated HSC (myofibroblast) Extracellular matrix (ECM) Krenkel O & Tacke F. Nat Rev Immunol 2017
18 Chemokine receptor CCR2/5-inhibitor CVC in experimental NASH and fibrosis Sirius Red [%] Liver Leukocytes [%] Mouse model of NASH (MCD) clinical trial phase 2b (ongoing) liver macrophages reduced patients with NASH + fibrosis (n=289) enriched for co-morbidities CVC 150mg (n=145) Placebo (n=144) WT 8w MCD Vhc. CVC liver biopsy after 1 year liver fibrosis reduced CVC 150mg (n=145) CVC 150 (n>63) Placebo (n>63) liver biopsy after 2 years WT 8w MCD Vhc. CVC Püngel T, Krenkel O, Tacke F. EASL 2016 NCT ; EudraCT number ; Sponsor: Tobira / Allergan
![Chemokine receptor CCR2/5-inhibitor CVC in experimental NASH and fibrosis Sirius Red [%] Liver Leukocytes [%] Mouse model of NASH (MCD) clinical trial phase 2b (ongoing) liver macrophages](/docs-images/77/75513897/images/19-6.jpg "reduced patients with NASH + fibrosis (n=289) enriched for co-morbidities CVC 150mg (n=145) Placebo (n=144) WT 8w MCD Vhc. CVC liver fibrosis reduced WT 8w MCD Vhc.")
19 Chemokine receptor CCR2/5-inhibitor CVC in experimental NASH and fibrosis Sirius Red [%] Liver Leukocytes [%] Mouse model of NASH (MCD) clinical trial phase 2b (ongoing) liver macrophages reduced patients with NASH + fibrosis (n=289) enriched for co-morbidities CVC 150mg (n=145) Placebo (n=144) WT 8w MCD Vhc. CVC liver fibrosis reduced WT 8w MCD Vhc. CVC Püngel T, Krenkel O, Tacke F. EASL 2016 liver biopsy after 1 year interim CVC 150mg analysis after CVC 1150 year Placebo treatment: (n=145) sufficient (n>63) paired (n>63) biopsies - baseline characteristics: 33% F1, liver 29% biopsy F2, 38% after F3 2 years fibrosis 52% type 2 diabetes, BMI ~34 kg/m² Sanyal A et al. #LB-1, AASLD 2016 NCT ; EudraCT number ; Sponsor: Tobira / Allergan
20 Chemokine receptor CCR2/5-inhibitor CVC in patients with NASH and fibrosis Percent of Subjects (%) Steatohepatitis-Score Fibrosis-Score Placebo (N=144) CVC (N=145) 25% 20% 19% 16% 15% 10% 25% 20% 15% 10% 10% P = % 5% 5% 0% 2-point Improvement in NAS AND No Worsening of Fibrosis 0% Improvement in Fibrosis Stage AND No Worsening of NASH NASH resolution: 8% vs. 6% (n.s.) Sanyal AJ, et al. AASLD 2016, #LB-1
21 Chemokine receptor CCR2/5-inhibitor CVC in patients with NASH and fibrosis Percent of Subjects (%) Response by Baseline Fibrosis Stage (mitt) 50% P = P = P = % 14% P = % 23% 20% 32% 16% 28% 0% n=44 n=42 n=35 n=34 n=47 n=50 n=82 n=84 Stage 1 Stage 2 Stage 3 Stage 2-3 Placebo CVC Sanyal AJ, et al. AASLD 2016, #LB-1
22 Monocyte / macrophage subsets during regression of liver fibrosis inflammatory Ly6C high monocyte Can we therapeutically provoke this phenotypic switch? fibrogenic Ly6C+ macrophage PDGF, TGFb, TNF, IL-1b TRAIL, MMP9/12/13 restorative Ly6C low macrophage HSC apoptosis Hepatic stellate cell (HSC) activated HSC (myofibroblast) reverted HSC Extracellular matrix (ECM) Krenkel O & Tacke F. Nat Rev Immunol 2017 Ramachandran P / Iredale J, PNAS Troeger JS / Schwabe RF, Gastroenterology Baeck C / Tacke F, Hepatology 2014
23 Targeting macrophages in liver inflammation and fibrosis Microbubbles Liposomes Polymers Ergen C / Lammers T / Tacke F. Biomaterials 2017
24 Targeting macrophages in liver inflammation: Drug delivery systems Liposomes i.v. blue: Kupffer cells Microbubbles Liposomes Polymers Kupffer cells Monocytederived macrophages Ergen C / Lammers T / Tacke F. Biomaterials 2017
25 Targeting macrophages in liver inflammation: Proof-of-concept in fibrosis Dexamethasone-loaded Liposomes liver fibrosis Bartneck M / Tacke F, Nanomedicine 2014 Bartneck M / Tacke F. Biomaterials 2015 Bartneck M / Tacke F, ACS Nano 2012 Topuz F / Tacke F. Biomacromolecules 2017
26 Monocytes and macrophages in liver diseases Acute liver injury NASH and fibrosis Immunometabolism
27 Immunometabolism 1: Integration of metabolic signals by macrophages Krenkel O & Tacke F. Nat Rev Immunol 2017;17(5):
28 Immunometabolism 2: Adaptation of cellular metabolism by macrophages Manifold potential targets PPAR α / / d ASK1 NF-κB activation glycolysis ROS and NO production distinct transcription factors inflammasome formation cytokine production Krenkel O & Tacke F. Seminars Liver Disease 2017 (in press)
29 Thank you! Tacke Lab Dr. Jana Mossanen Dr. Felix Heymann Dr. Matthias Bartneck Dr. Anke Liepelt Dr. Alexander Wehr Elham Shirvani-Dastgerdi Patricia Niemietz Klaudia Warzecha Julia Peusquens Oliver Krenkel Aline Roggenkamp Tobias Püngel Peter Schrammen Can Ergen Marlene Kohlhepp Q3 cell isolation Sibille Sauer-Lehnen Carmen Tag collaborators Aachen Tom Lüdde Christian Trautwein Thomas Longerich Ralf Weiskirchen Ulf Neumann collaborators Tania Roskams Olivier Govaere Quentin Anstee Eric Lefebvre Florent Ginhoux Steffen Jung Jo van Ginderachter Funding KMU-innovativ SFB/TRR57 Organ fibrosis Industry (Noxxon, Tobira/Allergan) Gwen Randolph
30 Role of macrophages in disease development and progression of NASH Monocyte and macrophage subsets impact inflammation, hepatocyte injury, hepatic stellate cell activation, angiogenesis, but also resolution of injury, in mice and men Hepatic macrophage heterogeneity in includes origin, differentiation/ polarization, immunological properties and functions in disease progression/regression Therapeutic application of the CCR2/CCR5 inhibitor CVC in mice ameliorates steatohepatitis and fibrosis without impairing tissue repair, supporting the therapeutic potential in patients with NASH Important lines of research in the field: regulation and balance of pro- and antiinflammatory subsets, novel imaging approaches to dissect immune cell subsets, immune mechanisms in transition from chronic inflammation to cancer, targeting mechanisms by nanoparticles, translation into clinics (biomarkers + therapy)
Liver Fibrosis: Which Mechanisms Matter?
REVIEW Liver Fibrosis: Which Mechanisms Matter? Ralf Weiskirchen, Ph.D.,* and Frank Tacke, M.D., Ph.D. HEPATIC FIBROSIS Historically, fibrosis was defined by a World Health Organization expert group in
Antifibrotic therapy: between hopes and reality. Fabio Marra Dipartimento di Medicina Sperimentale e Clinica University of Florence, Italy
Antifibrotic therapy: between hopes and reality Fabio Marra Dipartimento di Medicina Sperimentale e Clinica University of Florence, Italy Disclosures Abbvie: consultant fees AstraZeneca: consultant fees
An Update on the Pharmacological Treatment of Nonalcoholic Fatty Liver Disease: Beyond Lifestyle Modifications
REVIEW An Update on the Pharmacological Treatment of Nonalcoholic Fatty Liver Disease: Beyond Lifestyle Modifications Naim Alkhouri, M.D.,*, and Andrea Scott, B.S.* Nonalcoholic fatty liver disease (NAFLD)
Cenicriviroc Treatment for Adults with Non-Alcoholic Steatohepatitis: Year 2 Analysis of the Phase 2b
Cenicriviroc Treatment for Adults with Non-Alcoholic Steatohepatitis: Year 2 Analysis of the Phase 2b CENTAUR Study Vlad Ratziu, Arun Sanyal, Sven Francque, Vincent Wai-Sun Wong, Rohit Loomba, Zachary
Nonalcoholic Fatty Liver Disease in Children: Typical and Atypical
Nonalcoholic Fatty Liver Disease in Children: Typical and Atypical Disclosure Naim Alkhouri, MD discloses the following relationships with commercial companies: Membership in the Speakers Bureau for Alexion
Mechanisms of hepatic fibrogenesis in chronic liver disease
Mechanisms of hepatic fibrogenesis in chronic liver disease JPEMS 2014, Physiopathology Module Corentin Bessy (Nantes) _ Gabrielle Cepella (Amsterdam) _ Charly Gaisne (Angers) _ Gwladys Guilloineau (Angers)
Understanding Root Cause: Pathogenesis of Hepatic Fibrosis
10/1/12 Understanding Root Cause: Pathogenesis of Hepatic Fibrosis Hepatitis C Virus Mild inflammation Inflammation Fibrosis Cirrhosis 1 10/1/12 Non-alcoholic Fatty Liver Disease Steatosis Steatohepatitis
Liver-Resident Macrophage Necroptosis Orchestrates Type 1 Microbicidal Inflammation and Type-2- Mediated Tissue Repair during Bacterial Infection
Liver-Resident Macrophage Necroptosis Orchestrates Type 1 Microbicidal Inflammation and Type-2- Mediated Tissue Repair during Bacterial Infection Camille Blériot, Théo Dupuis, Grégory Jouvion, Gérard Eberl,
Liver fibrosis is a characteristic consequence of
Pharmacological Inhibition of the Chemokine C-C Motif Chemokine Ligand 2 (Monocyte Chemoattractant Protein 1) Accelerates Liver Fibrosis Regression by Suppressing Ly-6C 1 Macrophage Infiltration in Mice
WHAT THE EXPERIMENTAL MODELS CAN TEACH US IN NAFLD/NASH? Claudio Tiribelli, MD PhD Scientific Director FIF
WHAT THE EXPERIMENTAL MODELS CAN TEACH US IN NAFLD/NASH? Claudio Tiribelli, MD PhD Scientific Director FIF ctliver@fegato.it Worldwide estimated prevalence of NAFLD distribution of PNPLA3 genotypes 2017-Younussi
Alcoholic hepatitis is a drug-induced disorder
Alcoholic hepatitis is a drug-induced disorder Gyongyi Szabo, MD, PhD Professor of Medicine University of Massachusetts Medical School Source: 2 Sobernation.com Clinical Progression of ALD Mortality Acute
Fibrosis is a highly conserved response to hepatic
NEW HORIZONS Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways Ekihiro Seki 1,2 and Robert F. Schwabe 3,4 Inflammation is one of the most characteristic features of chronic liver disease
Forward-looking Statements
NASDAQ:CNAT Forward-looking Statements This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements
NASH Bench to Bedside
NASH Bench to Bedside October 2006 Anna Mae Diehl, M.D. Gastroenterology Division Duke University NonAlcoholic Fatty Liver Disease Common ~1/4-1/3 1/3 US adults Outcome highly variable Course indolent
Molecular mechanisms of Fibrosis: Targets of Therapy. John P Iredale University of Edinburgh, UK
Molecular mechanisms of Fibrosis: Targets of Therapy John P Iredale University of Edinburgh, UK Take home messages: The wound healing MFBs of the liver and the hepatic macrophages are key players in progressive
Chronic inflammation is the key factor promoting
Chemokine Receptor CCR6-Dependent Accumulation of cd T Cells in Injured Liver Restricts Hepatic Inflammation and Fibrosis Linda Hammerich, 1 J org M. Bangen, 1 Olivier Govaere, 2 Henning W. Zimmermann,
Role of Inflammatory and Progenitor Cells in Pulmonary Vascular Remodeling: Potential Role for Targeted Therapies. Traditional Hypothesis Stress
3/1/212 Role of Inflammatory and Progenitor Cells in Pulmonary Vascular Remodeling: Potential Role for Targeted Therapies K.R. Stenmark University of Colorado Denver, CO 845 Prominent Fibroproliferative
Reviewers' comments: Reviewer #1 (Remarks to the Author):
Reviewers' comments: Reviewer #1 (Remarks to the Author): The manuscript by Wu et al describes critical role of RNA binding protein CUGBP1 in the development of TGF-beta-mediated liver fibrosis. The activation
Study Design to Validate Biomarkers of Therapeutic Response in NASH Due to Cirrhosis
Study Design to Validate Biomarkers of Therapeutic Response in NASH Due to Cirrhosis Detlef Schuppan Institute of Translational Immunology and Research Center for Immune Therapy, University Medical Center
Macrophage derived Wnt signalling opposes Notch signalling in a Numb mediated manner to specify HPC fate in chronic liver disease in human and mouse.
Macrophage derived Wnt signalling opposes Notch signalling in a Numb mediated manner to specify HPC fate in chronic liver disease in human and mouse. Luke Boulter, Olivier Govaere, Tom G Bird, Sorina Radulescu,
EARLY INFLAMMATORY RESPONSES TO VASCULAR DEVICES
EARLY INFLAMMATORY RESPONSES TO VASCULAR DEVICES JAMES M. ANDERSON, MD, PhD DISTINGUISHED UNIVERSITY PROFESSOR DEPARTMENTS OF PATHOLOGY, MACROMOLECULAR SCIENCE, AND BIOMEDICAL ENGINEERING CASE WESTERN
PD-L1 Expression and Signaling by Tumors and Macrophages: Comparative Studies in Mice and Dogs
PD-L1 Expression and Signaling by Tumors and Macrophages: Comparative Studies in Mice and Dogs Steven Dow, DVM, PhD Department of Clinical Sciences, Animal Cancer Center Colorado State University Consortium
Role of macrophages in experimental liver injury and repair in mice (Review)
EXPERIMENTAL AND THERAPEUTIC MEDICINE Role of macrophages in experimental liver injury and repair in mice (Review) XIAOTIAN DONG, JINGQI LIU, YANPING XU and HONGCUI CAO State Key Laboratory for Diagnosis
Advances in Understanding Hepatic Fibrosis and Chronic Liver Disease
Advances in Understanding Hepatic Fibrosis and Chronic Liver Disease Scott Friedman, M.D. Fishberg Professor of Medicine Dean for Therapeutic Discovery Chief, Division of Liver Diseases Icahn School of
Disclosures. Outline. Extracellular Vesicles in Fatty Liver Disease. From Contributors to disease pathogenesis to novel biomarkers
Extracellular Vesicles in Fatty Liver Disease From Contributors to disease pathogenesis to novel biomarkers Ariel Feldstein, M.D. Professor of Pediatrics Chief, Division of Pediatric Gastroenterology Hepatology
The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases
Wermuth and Jimenez Clinical and Translational Medicine (2015) 4:2 DOI 10.1186/s40169-015-0047-4 REVIEW The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human
Materials and Methods HUMAN LIVER SAMPLES
AMERICAN ASSOCIATION FOR THE STUDY OFLIVERD I S E ASES HEPATOLOGY, VOL. 63, NO. 4, 2016 LIVER INJURY/REGENERATION Histidine-Rich Glycoprotein Promotes Macrophage Activation and Inflammation in Chronic
Supplemental Table 1. Primer sequences for transcript analysis
Supplemental Table 1. Primer sequences for transcript analysis Primer Sequence (5 3 ) Primer Sequence (5 3 ) Mmp2 Forward CCCGTGTGGCCCTC Mmp15 Forward CGGGGCTGGCT Reverse GCTCTCCCGGTTTC Reverse CCTGGTGTGCCTGCTC
Disease Burden of Non Alcoholic Fatty Liver Disease (NAFLD)
Disease Burden of Non Alcoholic Fatty Liver Disease (NAFLD) Dr. H. Razavi May 31, 2017 First European NASH NAFLD Summit Disclosure: This work with funded by a multi-sponsored research grant from Intercept,
Targeting tumour associated macrophages in anti-cancer therapies. Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018
Targeting tumour associated macrophages in anti-cancer therapies Annamaria Gal Seminar Series on Drug Discovery Budapest 5 January 2018 Macrophages: Professional phagocytes of the myeloid lineage APC,
Update on Nonalcoholic Fatty Liver Disease. Kathleen E Corey, MD, MPH, MMSc Director, Mass General Fatty Liver Clinic
Update on Nonalcoholic Fatty Liver Disease Kathleen E Corey, MD, MPH, MMSc Director, Mass General Fatty Liver Clinic Outline Defining the phenotypes of nonalcoholic fatty liver disease NAFLD Diagnostics
Myeloid Cell Immunology: Global strategy
Myeloid Cell Immunology: Global strategy Myeloid Cell Immunology: Model systems Infectious inflammation: Listeria Lung, Trypanosoma Brain Inflammation Serge Muyldermans (Nanobodies) Infectious inflammation:
IL-17 in health and disease. March 2014 PSO13-C051n
IL-17 in health and disease March 2014 PSO13-C051n Originally Researchers Suggested That IL-12 and IL-4 drove Th Cell Differentiation Naïve CD4 + T cell Question: Which of these cell types is responsible
A pathologist, a radiologist and a hepatologist walked into a bar
A pathologist, a radiologist and a hepatologist walked into a bar Brent A. Neuschwander-Tetri, MD, FAASLD Professor of Internal Medicine Director, Division of Gastroenterology and Hepatology Saint Louis
Manipulating the Tumor Environment
Manipulating the Tumor Environment Vincenzo Bronte Verona University Hospital vincenzo.bronte@univr.it Escape from immune control can be viewed as one of the «Hallmarks of Cancer» D. Hanahan and R. A.
EASL International Liver Congress Paris, France 14 April 2018
NGM282 Improves Fibrosis and NASH-Related Histology in 12 Weeks in Patients With Biopsy-Confirmed NASH, Which is Preceded By Significant Decreases in Hepatic Steatosis, Liver Transaminases and Fibrosis
Sustained inflammation is a common characteristic
LIVER FAILURE/CIRRHOSIS/PORTAL HYPERTENSION The Fractalkine Receptor CX 3 CR1 Protects Against Liver Fibrosis by Controlling Differentiation and Survival of Infiltrating Hepatic Monocytes Karlin Raja Karlmark,
DIA Oligonucleotide-Based Therapeutics Conference
DIA Oligonucleotide-Based Therapeutics Conference North Bethesda MD October 25-27 Translating PD Biomarkers From Preclinical Studies to Clinical Trials: MRG-201, an Oligonucleotide Mimic of mir- 29, Inhibits
Fabio Marra Dipartimento di Medicina Sperimentale e Clinica University of Florence, Italy
I tests biochimici nella valutazione dell infiammazione e fibrosi epatica Fabio Marra Dipartimento di Medicina Sperimentale e Clinica University of Florence, Italy fabio.marra@unifi.it Abbvie: consultant
Non-alcoholic fatty liver disease: time to take note and manage. Philip Newsome Professor of Hepatology & Director of Centre for Liver Research
Non-alcoholic fatty liver disease: time to take note and manage Philip Newsome Professor of Hepatology & Director of Centre for Liver Research Disclosures Consultancy, Co-ordinating Investigator roles
Research in IBD at University of Colorado Denver
Research in IBD at University of Colorado Denver Blair Fennimore, MD Assistant Professor of Medicine Division of Gastroenterology and Hepatology UCH Crohn s and Colitis Center Mucosal Inflammation Program
Extracellular vesicles and ceramide: new mediators for macrophage chemotaxis? Natalie J. Torok
Extracellular vesicles and ceramide: new mediators for macrophage chemotaxis? Natalie J. Torok Department of Medicine, Gastroenterology and Hepatology, UC Davis, Sacramento, CA, and Northern California
Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants With Mild or Moderate Hepatic Impairment
Citation: Clin Transl Sci (2016) 9, 139 148; C 2016 ASCPT. All rights reserved. doi:10.1111/cts.12397 PHASE FORWARD Pharmacokinetics, Safety, and CCR2/CCR5 Antagonist Activity of Cenicriviroc in Participants
Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology
Review Article: Liver Immunology Cellular and molecular functions of hepatic stellate cells in inflammatory responses and liver immunology Ralf Weiskirchen 1, Frank Tacke 2 1 Institute of Molecular Pathobiochemistry,
?Who binds to it. ? Who binds these inflammatory proteins RAGE SUGAR-FREE GLYCOBIOLOGY INFLAMMATION. BASIC SCIENCE?sugar chain structure
SUGAR-FREE GLYCOBIOLOGY BASIC SCIENCE?sugar chain structure Unusual Sugar Chain It -- is a carboxylate Make lots of It Make an It antibody Inflammatory proteins?who binds to it? Who binds these inflammatory
Innate Immune Consequences of Hepatocyte Injury. Katherine J. Brempelis. A dissertation. submitted in partial fulfillment of the
Innate Immune Consequences of Hepatocyte Injury Katherine J. Brempelis A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy University of Washington
Role of Inflammation in Pulmonary Hypertension
Role of Inflammation in Pulmonary Hypertension K. R. Stenmark University of Colorado Denver, USA Prominent Fibroproliferative Changes are Observed in the Lung Vasculature of Infants With Pulmonary Arterial
National Cancer Institute 1
Radioprotectors and Mitigators for Improving Radiotheapy July 31-Aug. 4, 2016 Pataje G. Prasanna, PH.D. C. Norman Coleman, M.D. Radiation Research Program National Cancer Institute/NIH E-mail: pat.prasanna@nih.gov
COPD: From Phenotypes to Endotypes. MeiLan K Han, M.D., M.S. Associate Professor of Medicine University of Michigan, Ann Arbor, MI
COPD: From Phenotypes to Endotypes MeiLan K Han, M.D., M.S. Associate Professor of Medicine University of Michigan, Ann Arbor, MI Presenter Disclosures MeiLan K. Han Consulting Research support Novartis
Update on Non-Alcoholic Fatty Liver Disease. Timothy R. Morgan, MD Chief, Hepatology, VA Long Beach Professor of Medicine, UCI
Update on Non-Alcoholic Fatty Liver Disease Timothy R. Morgan, MD Chief, Hepatology, VA Long Beach Professor of Medicine, UCI February 3, 2018 Disclosure Clinical trials: Genfit Speaker s Bureau: none
SERUM HBV-RNA LEVELS DECLINE SIGNIFICANTLY IN CHRONIC HEPATITIS B PATIENTS DOSED WITH THE NUCLEIC-ACID POLYMER REP 2139-Ca
SERUM HBV-RNA LEVELS DECLINE SIGNIFICANTLY IN CHRONIC HEPATITIS B PATIENTS DOSED WITH THE NUCLEIC-ACID POLYMER REP 2139-Ca Louis Jansen 1,2, Andrew Vaillant 3, Karel van Dort 1, Femke Stelma 1,2, Neeltje
METABOLIC SYNDROME AND HCV: FROM HCV
METABOLIC SYNDROME AND HCV: FROM THEORY TO PRACTICE HCV Steatosis Insulin resistance Arun J Sanyal M.D. Chairman, Div. of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University Richmond,
The Enhancement of Toxin-Induced Liver Fibrosis in Fatty Liver Disease. Ekihiro Seki, M.D.,Ph.D. University of California San Diego
The Enhancement of Toxin-Induced Liver Fibrosis in Fatty Liver Disease Ekihiro Seki, M.D.,Ph.D. University of California San Diego - A manufactured chemical. - Does not exist naturally. Carbon tetrachloride
Roger J. Davis. Metabolic Stress Signaling by the JNK Pathway
Roger J. Davis Metabolic Stress Signaling by the JNK Pathway Age-adjusted Percentage of U.S. Adults with Diagnosed Diabetes or Obesity Diabetes 1994 2000 2007 Obesity (BMI 30 kg/m 2 )
Liver cirrhosis following chronic liver inflammation
Hepatic Macrophage Migration and Differentiation Critical for Liver Fibrosis Is Mediated by the Chemokine Receptor C-C Motif Chemokine Receptor 8 in Mice Felix Heymann, 1 Linda Hammerich, 1 Dunja Storch,
Evercore ISI Presentation- Madrigal
Evercore ISI Presentation- Madrigal Forward-Looking Statements Any statements, other than statements of historical facts, made in this presentation regarding our clinical studies and our research and development
Non-Invasive Assessment of Liver Fibrosis. Patricia Slev, PhD University of Utah Department of Pathology
Non-Invasive Assessment of Liver Fibrosis Patricia Slev, PhD University of Utah Department of Pathology Disclosure Patricia Slev has no relevant financial relationships to disclose. 2 Chronic Liver Disease
Reversal of liver cirrhosis: current evidence and expectations
REVIEW Korean J Intern Med 2017;32:213-228 https://doi.org/10.3904/kjim.2016.268 Reversal of liver cirrhosis: current evidence and expectations Young Kul Jung and Hyung Joon Yim Division of Gastroenterology
Bile Acids and Liver Fibrosis Causative Agent and Therapeutic Tool
Bile Acids and Liver Fibrosis Causative Agent and Therapeutic Tool Peter Fickert, Andrea Fuchsbichler, Tarek Moustafa, Gernot Zollner, Emina Halilbasic, Ulrike Stöger, Cord Langner, Helmut Denk, and Michael
Nottingham Patterns of liver fibrosis and their clinical significance
Nottingham 2006 Patterns of liver fibrosis and their clinical significance Alastair D Burt Professor of Pathology and Dean of Clinical Medicine University of Newcastle upon Tyne Collapse of reticulin
Company Overview. September 2018 NASDAQ: MDGL
Company Overview September 2018 NASDAQ: MDGL 1 Forward Looking Statements Any statements, other than statements of historical facts, made in this presentation regarding our future financial or business
Fatty Liver Disease A growing epidemic
Fatty Liver Disease A growing epidemic Updates in GIM for Primary Care Don C. Rockey March 9 th, 2018 Disclosures 2018 Research Funding (all to MUSC) NIH/NIDDK Actelion Pharmaceuticals Gilead Sciences
Laura Smart 9/22/2011
Laura Smart 9/22/2011 Fibrosis is a wound healing response in which damaged regions are encapsulated by an extracellular matrix or scar. Fibrosis develops in almost all patients with chronic liver injury
Immunological Lung Diseases
Emphysema and Fibrosis Universitätsklinik für Pneumologie Prof. Thomas Geiser Head Div. of Pulmonary Medicine and Laboratory of Lung Research, MU50 thomas.geiser@insel.ch The healthy lung: The pathway
Fatty Liver- how important is it? Jeremy F.L. Cobbold MA PhD MRCP Clinical Lecturer in Hepatology Imperial College London
Fatty Liver- how important is it? Jeremy F.L. Cobbold MA PhD MRCP Clinical Lecturer in Hepatology Imperial College London Fatty liver- how important is it? Importance in terms of: Prevalence Pathogenesis
Hepatitis D. Challenges in 2018
Hepatitis D Challenges in 2018 Heiner Wedemeyer Essen University Hospital, Germany Germany Disclosures Honoraria for consulting or speaking (last 5 years): Abbott, AbbVie, Abivax, BMS, Boehringer Ingelheim,
Journal Club Semmler Lorenz
Beer et al. 2015 - Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration Journal Club 13.11.2017 1 Introduction to
Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document.
Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury Rantakari, Pia; Patten, Daniel; Valtonen, Joona; Karikoski, Marika; Gerke,
ROLE OF INFLAMMATION IN HYPERTENSION. Dr Barasa FA Physician Cardiologist Eldoret
ROLE OF INFLAMMATION IN HYPERTENSION Dr Barasa FA Physician Cardiologist Eldoret Outline Inflammation in CVDs the evidence Basic Science in Cardiovascular inflammation: The Main players Inflammation as
Division of Gastroenterology, Hepatology and Nutrition Research. Research. Matthew Cave, M.D. Cave Research. Cave Research
Division of Gastroenterology, Hepatology and Nutrition Matthew Cave, M.D. Cave Industry Sponsored Clinical Trials Merck (hepatitis C protease inhibitor) Intercept (PBC FXR agonist) Sucampo (Wo, cytokines
NAFLD & NASH: Russian perspective
NAFLD & NASH: Russian perspective Vasily Isakov, MD, PhD Professor, Chief, Department Gastroenterology & Hepatology, Federal Research Center of nutrition, biotechnology and food safety Disclosures Received
NASH Regulatory Landscape. Veronica Miller, PhD Forum for Collaborative Research UC Berkeley SPH
NASH Regulatory Landscape Veronica Miller, PhD Forum for Collaborative Research UC Berkeley SPH Disclosures Liver Forum sponsors (last slides) Advisory (Sanofi) Miller_July 7_2017 www.forumresearch.org
Dietary supplementation in treating non-alcoholic fatty liver disease Dr. Ahmad Saedi Associate Professor School of Nutritional Sciences and
Dietary supplementation in treating non-alcoholic fatty liver disease Dr. Ahmad Saedi Associate Professor School of Nutritional Sciences and Dietetics Tehran University of Medical Sciences Honorary Academic
Effector T Cells and
1 Effector T Cells and Cytokines Andrew Lichtman, MD PhD Brigham and Women's Hospital Harvard Medical School 2 Lecture outline Cytokines Subsets of CD4+ T cells: definitions, functions, development New
Supplementary Information. Tissue-wide immunity against Leishmania. through collective production of nitric oxide
Supplementary Information Tissue-wide immunity against Leishmania through collective production of nitric oxide Romain Olekhnovitch, Bernhard Ryffel, Andreas J. Müller and Philippe Bousso Supplementary
Bariatric Surgery and Liver Transplantation
Bariatric Surgery and Liver Transplantation Sammy Saab, MD, MPH, AGAF, FACG, FAASLD Professor of Medicine and Surgery Head, Outcomes Research in Hepatology David Geffen School of Medicine at UCLA Disclosures
SUPPLEMENTARY INFORMATION
doi:10.1038/nature10134 Supplementary Figure 1. Anti-inflammatory activity of sfc. a, Autoantibody immune complexes crosslink activating Fc receptors, promoting activation of macrophages, and WWW.NATURE.COM/NATURE
The Effect of Antiviral Therapy on Liver Fibrosis in CHC. Jidong Jia Beijing Friendship Hospital, Capital Medical University
The Effect of Antiviral Therapy on Liver Fibrosis in CHC Jidong Jia Beijing Friendship Hospital, Capital Medical University 2016-5-29 1 Disclosure Consultation for Abbvie, BMS, Gilead, MSD, Novartis and
Lipid and Bile Acids as NAFLD- Related Biomarkers
Lipid and Bile Acids as NAFLD- Related Biomarkers Puneet Puri, MBBS, MD Division of Gastroenterology, Hepatology and Nutrition Virginia Commonwealth University, Richmond, VA 1st International Workshop
Insights into the Cell-of-Origin of the Histiocytoses Using Patient-Derived Xenograft Models
Insights into the Cell-of-Origin of the Histiocytoses Using Patient-Derived Xenograft Models 4 th Annual International Erdheim-Chester Disease Medical Symposium Paris, France September 15, 2016 Benjamin
Uncovering the mechanisms of wound healing and fibrosis
Any Questions??? Ask now or contact support support@sabiosciences.com 1-888-503-3187 International customers: SABio@Qiagen.com Uncovering the mechanisms of wound healing and fibrosis Webinar related questions:
The Role of Innate Immunity in Alcoholic Liver Disease
ALCOHOL RESEARCH: Current Reviews The Role of Innate Immunity in ic Liver Disease Laura E. Nagy, Ph.D. Laura E. Nagy, Ph.D., is a professor of molecular medicine at Case Western Reserve University School
Study Design to Validate Biomarkers of Therapeutic Response in Pre-cirrhotic NASH
Study Design to Validate Biomarkers of Therapeutic Response in Pre-cirrhotic NASH Brent A. Neuschwander-Tetri, MD, FAASLD Professor of Internal Medicine Director, Division of Gastroenterology and Hepatology
ADME in NAFLD: Genes and Big Jeans Increase the Risk of Adverse Drug Reactions. Drug-Induced Liver Injury
ADME in NAFLD: Genes and Big Jeans Increase the Risk of Adverse Drug Reactions Nathan J. Cherrington, Ph.D. Drug-Induced Liver Injury Minimal Toxicity Toxicity Exposure 1 Obesity: An Increasing Health
Autoimmune Diseases. Betsy Kirchner CNP The Cleveland Clinic
Autoimmune Diseases Betsy Kirchner CNP The Cleveland Clinic Disclosures (financial) No relevant disclosures Learning Objectives Explain the pathophysiology of autoimmune disease Discuss safe administration
HepaRG LX2. HepaRG HepaRG LX2 LX2
C Supporting Figure 1. Experimental design of s between and cells. (A) -hepatocytes were isolated from a 30 days of -progenitors. Differentiation into mature hepatocytes was achieved following a 2-weeks
Topical nanocrystalline silver cream inhibits expression of matrix metalloproteinase-9 in animal models of allergic contact dermatitis.
Topical nanocrystalline silver cream inhibits expression of matrix metalloproteinase-9 in animal models of allergic contact dermatitis. K C Bhol, P J Schechter NUCRYST Pharmaceuticals Inc, Wakefield, MA
Mononuclear Phagocytes - Origins, Fates & Functions - Dr. Steffen Jung
1 Department of Immunology The Weizmann Institute of Science Rehovot, Israel The mononuclear phagocyte system Van Furth and Cohn (1968) Ilya (Eli) Metchnikoff (1845-1916) Nobel prize 1908 Macrophages Ralph
Cholesterol and Sphingolipids in Non-Alcoholic fatty liver disease.
Cholesterol and Sphingolipids in Non-Alcoholic fatty liver disease. José C. Fernández-Checa Liver Unit, Hospital Clinic CIBEK and IDIBAPS Instituto Investigaciones Biomédicas Barcelona Consejo Superior
Mark D Gorrell Sumaiya Chowdhury, Fiona Keane, Stephen Twigg, Geoff McCaughan
The protease fibroblast activation protein [FAP] as a biomarker and therapeutic target in chronic liver injury Mark D Gorrell Sumaiya Chowdhury, Fiona Keane, Stephen Twigg, Geoff McCaughan A.W. Morrow
SOMATOSTATIN RECEPTORS IN HEPATOCELLULAR CARCINOMA. Marie LEQUOY Saint-Antoine Hospital, Department of Hepatology, Paris, France
SOMATOSTATIN RECEPTORS IN HEPATOCELLULAR CARCINOMA Marie LEQUOY Saint-Antoine Hospital, Department of Hepatology, Paris, France Somatostatin : SST Somatostatin (SST) protein : 2 active forms (alternative
EASL EASD EASO Clinical practice guidelines for the management of nonalcoholic fatty liver disease.
Commentary. EASL EASD EASO Clinical practice guidelines for the management of nonalcoholic fatty liver disease. Christopher D. Byrne 1,2, Giovanni Targher 3 1 Nutrition and Metabolism, Faculty of Medicine,
The Role of Chemokines in Hepatitis C Virus-Mediated Liver Disease
Int. J. Mol. Sci. 2014, 15, 4747-4779; doi:10.3390/ijms15034747 Review OPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 www.mdpi.com/journal/ijms The Role of Chemokines in Hepatitis
DECLARATION OF CONFLICT OF INTEREST. No conflicts of interest
DECLARATION OF CONFLICT OF INTEREST No conflicts of interest University Heart Centre Tübingen Angiogenic actions of platelets Meinrad Gawaz, MD, FESC Tübingen, Germany ESC 2011 Paris GPIb GPIb GPVI TxA2
removed replaced inflammation scar tissue
HOMEOSTASIS Normal maintenance and renewal of differentiated cells in many tissues This does NOT involve leukocytes. Leukocytes and inflammation occurs in response to damage NEED FOR REPAIR When tissue
The innate immune receptor TREM-1 promotes liver injury and fibrosis
The innate immune receptor TREM-1 promotes liver injury and fibrosis Anh Thu Nguyen-Lefebvre,, Giorgio Trinchieri, Anatolij Horuzsko J Clin Invest. 2018. https://doi.org/10.1172/jci98156. Research In-Press
Macrophages in Nonalcoholic Steatohepatitis: Friend or Foe?
Macrophages in Nonalcoholic Steatohepatitis: Friend or Foe? Authors: Joel Grunhut, 1 Wei Wang, 1 Berk Aykut, 1 Inderdeep Gakhal, 1 Alejandro Torres-Hernandez, 1 *George Miller 1,2 1. S.A. Localio Laboratory,
ACR Meeting November, 2012
ACR Meeting November, 212 Arhalofenate is a Novel Dual-Acting Agent with Uricosuric and Anti-Inflammatory Properties Yun-Jung Choi, Vanina Larroca, Annette Lucman, Vic Vicena, Noe Abarca, Tim Rantz, Brian
2 nd International Workshop on NASH Biomarkers, Washington DC, May 5-6, 2017
Hepatic Proton Density Fat Fraction Correlates With Histologic Measures of Steatosis and Is Responsive to Changes in Those Measures in a Multi-center Nonalcoholic Steatohepatitis Clinical Trial Michael
Liver inflammation and fibrosis
Liver inflammation and fibrosis Yukinori Koyama, David A. Brenner J Clin Invest. 2017;127(1):55-64. https://doi.org/10.1172/jci88881. Review Series Chronic liver inflammation leads to fibrosis and cirrhosis,