IgG. IgG. narrow-band UVB co-culture. E- P-cadherin PCNA. Abstract Vitiligo vulgaris is an acquired

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2 行 : B IgG (3/3) Title: Effects of narrow-band UVB and IgG antibodies from patients with vitiligo vulgaris on migrationproliferation and melanogenesis in melanocytes and melanoblasts (3/3) : NSC B 行 : 93 年 年 7 31 : 行 : 立. 罹 率 1-4% 不 IgG 年度 IgG narrow-band UVB co-culture E-P-cadherin 異 IgG PCNA IgG UVB DNA 復 力 療 SCF, SCF 度 力 : Abstract IgG DNA 復 復 Vitiligo vulgaris is an acquired dermyu@ha.mc.ntu.edu.tw depigmented disorder that affects 1~4 % of the population. Functional melanocytes in patients with vitiligo vulgaris disappear from involved skin by a mechanism(s) that has not yet been identified. An immunological hypothesis is currently proposed as a possible pathogenesis of non-segmental-type vitiligo. Coexistence of antimelanocyte and antikeratinocyte IgG antibodies were noticed in patients with vitiligo. The studies of this year was focus on the effects of narrow-band UVB and serum IgG of vitiligo patients or normal control melanocytes on keratinocytes in term of DNA repair and the expression of E P-cadherins The results revealed that the expression of E- and P-cadherin on the membrane of keratinocytes was not influenced by serum-igg/narrow-band UVB treatment. However, V-IgG significantly increased the expression of PCNA in the nuclear of narrow-band UVB treated keratinocytes. This result suggests that the patients serum IgG may protect keratinocyte from UVB damage. The low level of SCF in patients with vitiligo is another important finding 1

3 which indicates that a low melanocyte migration and proliferation activity in vitiligo patients. Keywords: melanocytekeratinocyte. vitiligo IgG antibodydna repairrepigmentation 不 罹 率 1-4%Koga 類 兩 [Koga, 1977] 神 異 異 Moellmann (1)(active stage)(2)(stable stage)(3) 復 (repigmenting stage) 不 不 度 [Moellmann et al., 1982]Naughton (vitiligo-associated melanocyte antigens) IgG [Naughton et al., 1983 (a) and (b)]norris 更 參 殺 [1988] 復 [Halaban et al., 1988; Gordon et al., 1989; Halder and Young, 2000] 不 見 UVB UVB 復 UVB DNA DNA 復 年度 臨 療 復. 行 1. [Yu et al., 1993] IgG 利 Saphacryl S-300 gel filtration 離 IgG fraction 冷 IgG [Yu et al., 1993] 4. 1:10 率 數 [Valyi-Nagy et al., 1990] (N-IgG) (V-IgG)IgG 100 g/ml 4 narrow-band UVB 0 50 mj/cm 2 IgG 24 行 E-P-cadherin PCNA 5. 療 療 療 15ml ELISA 行 mitogen. 論 2

4 1. 1:10 例 UVB N-IgG/V-IgUVB 理 immunocyochemistry 行 E-P-cadherinPCNA E- P-cadherin 不 理 異 ( 1A and B) PCNA 不 理 control 例 28.2 ± 5.6 %UVB 25 mj/cm 2 例 52.0 ± 6.7 % N-IgG/UVB 理 例 74.3 ± 10.8 %V-IgG/UVB 理 例 88.7 ± 12.7 % IgG UVB DNA 復 力 IgG IgG () 2. 療 SCF ( ) narrow-band UVB 療 UVB SCF 量 [Tao, 2000., Kihira, 1998] 度 力 3. 年度 IgG 刺 narrow-band UVB DNA damage - IgG IgG UVB DNA 復 力 melanin [Iyengar, 1998]. 參 Gordon P, Mansur C, Gilchrest B: Regulation of human melanocyte growth, dendricity, and melanization by keratinocyte derived factors. J Invest Dermatol 92: , Halaban R, Langdon R, Birchall N: Basic fibroblast growth factor from human keratinocytes is a natural mitogen for melanocytes. J Cell Biol 107: , Halder RM, Young CM: New and emerging therapies for vitiligo. Dermatol Clin 18; 79-89, Iyengar B: The role of melanocytes in the repair of UV related DNA damage in keratinocytes. Pigment Cell Res 11: , Kihira C, Mizutani H, Asahi K, Hamanaka H, Shimizu M. Increased cutaneous immunoreactive stem cell factor expression and serum stem cell factor level in systemic scleroderma. J Dermatol Sci.20: Koga M: Vitiligo: A new classification and therapy. Br J Dermatol 97: ,1977. Moellmann G, Kiein-Angfrer S, Scollay DA, Nordlund JJ, Lerner AB. Extracellular granular material and degeneration of keratinocytes in the normally pigmented epidermis of patients with vitiligo. J Invest Dermatol 79: , Naughton GK, Esinger M, Bystryn JC. 3

5 Antibodies to normal human melanocytes in vitiligo. J Exp Med 158: , 1983 (a). Naughton GK, Esinger M, Bystryn JC. Detection of antibodies to melanocytes by specific immunoprecipitation. J Invest Dermatol 81: , 1983 (b). Norris DA, Kissinger RM, Naughton GM. Evidence for immunologic mechanism in human vitiligo: Patients sera induced damage to human melanocytes in vitro by complement-mediated damage and antibody dependent cellular cytotoxicity. J Invest Dermatol 90: , Tao M, Li B, Nayini J, Andrews CB, Huang RW, Devemy E, Song S, Venugopal P, Preisler HD. SCF, IL-1beta, IL-1ra and GM-CSF in the bone marrow and serum of normal individuals and of AML and CML patients. Cytokine.12: (B) (B) 類 UVB 25 mj/cm 2 () N-IgG/UVB () V-IgG/UVB 理 P-cadherin Valyi-Nagy IT, Murphy GF, Mancianti ML, Whitaker D, Herlyn M: Phenotypes and interactions of human melanocytes and keratinocytes in an epidermal resconstruction model. Lab Invest 62: , (A). (A) 類 Percentage of PCNA positice cell (%) Control UVB (25 mj/cm2) N-IgG (100 ug/ml)+uvb (25 mj/cm2) V-IgG (100 ug/ml)+uvb (25 mj/cm2) UVB 25 mj/cm 2 () N-IgG/UVB () V-IgG/UVB 理 E-cadherin. 類 PCNA 200 例 *p<0.05, V-IgG/UVB group v.s. UVB group 4

6 Control UVB 25 mj/cm 2 irradiation N-IgG UVB 25 mj/cm 2 N-IgG V-IgG UVB 25 mj/cm 2 V-IgG. 類 PCNA Growth factors(pg/ml) SCF Before treatment ± Middle treatment ± After treatment ± Normal range:1201~1565(pg/ml) 療 SCF 度 (N=7) 5