자외선에 노출된 멜라닌세포성 모반에서 랑게르한스 세포 수와 사이토카인 발현에 관한 연구 = Langerhans Cells and Cytokines in UV-irradiated Melanocytic Nevi자외선에 노출된 멜라닌세포성 모반에서 랑게르한스 세포 수와 사이토카인 발현에 관한 연구

다국어 초록 (Multilingual Abstract)

Background: It is well established that UV-induced DNA damage is involved in the mutation of oncogenes and tumor suppressor genes, and the subsequent development of skin cancers. Langerhans cells (LC) are thought to play an important role in the presentation of tumor antigens for the induction of anti-tumor immunity. Cytokines may have a key role in the UV-induced modulation of the skin`s immune system. Objective: To clarify the role of Langerhans cells, cytokines in UV-irradiated Melanocytic Nevi vs non-irradiated melanocytic nevi. Methods: Skin biopsies from 10 melanocytic nevi, taken from partially covered melanocytic navi and irradiated part with a defined UV dose, were examined. Immunohistochemical staining was used for the quantitative distribution of LC and the expression of cytokines which are related to LC migration and maturation (TNF-α and GM-CSF), Th1 response (IL-12), and Th2 response (IL-10). Results: LC number increased in non-irradiated neoplastic epithelium compared to control skin. In UV-exposed nevi, LC density decreased significantly but a constant number was still maintained. TNF-α and GM-CSF were predominently expressed in lesional epithelium and some nevus cells, 2 days after irradiation. GM-CSF expression in nevus cells was maintained up to 7 days after exposure. IL-10 was expressed in epidermis 2 days after exposure. While IL-12 was weakly positive and maintained up to 7 days in unexposed lesional epidermis, it was not detected after 2 days but reappeared in an exposed lesion after 7 days. Conclusion: Langerhans cells (LC) modulated by cytokines in UV-exposed skin may have a functional role in UV-induced carcinogenesis. (Korean J Dermatol 2007;45(9):915∼922)

참고문헌 (Reference)

1 "is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med 1988" 1484-1498,

2 "et al. Human keratinocytes are a source for tumor necrosis factor α evidence for systhesis and release upon stimulation with endotoxin or ultraviolet light. J Exp Med 1990" 1609-1614,

3 "Ultaviolet B radiation induces a transient appearance of IL-4+ neutrophils, which support the development of Th2 responses" 168 : 3732-3739, 2002

4 "UVB induced apoptosis of keratinocytes. Evidence for partial involvement of tumor necrosis factor alpha in the formation of sunburn cells" 104 : 922-927, 1995

5 "Trinchieri G. Interleukin-12 and its role in the generation of Th1 cells. Immunol Today 1993" 335-338,

6 "Transforming growth factor-β produced by progressor tumors inhibits, while IL-10 produced by regressor tumors enhances, Langerhans cell migration from skin" 13 : 1147-1154, 2001

7 "Thivolet J. T cell subsets and Langerhans cells in skin tumors. Eur J Cancer Clin Oncol 1983" 907-913,

8 "TNF alpha interrupts antigen presenting function of Langerhans cells by two mechanisms: loss of immunogenic peptides and impairment of antigen-independent clustering" 378 : 207-209, 1995

9 "Rowden G. Quantitative assessment of Langerhans cells in actinic keratosis" 212-216,

10 "Reduced IL-12 production by monocyte upon ultraviolet-B irradiation selectively limits activation of T helper-1 cells" 157 : 1913-1918, 1996

11 "Muller HK. New methodology for assessment of the Langerhans' cell network. J Pathol 1986" 127-134,

12 "Moore KW. The role of IL-10 in crossregulation of TH1 and TH2 responses. Immunol Today 1993" -53,

13 "McCarthy WH. Immunohistochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma. J Invest Dermatol 1991" 197-202

14 "Mason DY. Langerhans' cells and T cells in human skin tumors" 229-244,

15 "Lisi P. Investigation of Langerhans' cells in pathological human epidermis. Acta Derm 425-428 cited from ref. 4" 1973

16 "Lim HW. Effect of glucocorticoids on epidermal Langerhans' cells J Exp Med 1982" 291-302,

17 "Knight BA. Carcinogen-induced deplition of cutaneous Langerhans' cells. Br J Cancer 1985" 81-85,

18 "Katz SI. The role of Langerhans' cells in immunity. Arch Dermatol 1980" 1361-1362,

19 "Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo and in vitro" 154 : 4851-4856, 1995

20 "In human skin, UVB initiates early induction of IL-10 over IL-12 preferentially in the expanding dermal monocytic/ macrophagic population" 111 : 31-38, 1998

21 "IL-10 inhibits tumor antigen presentation by epidermal antigen presenting cells" 154 : 1280-1286, 1995

22 "Granstein RD. Tumor antigen presentation by epidermal antigen- presenting cells in the mouse modulation by granulocyte- macrophage colony-stimulating factor" 209-217,

23 "Granstein RD. Mechanisms of ultraviolet radiation carcinogenesis. Chem Immunol 1994" 291-313,

24 "Friedmann PS. Disappearance of epidermal Langerhans' cells during PUVA Therapy. Br J Dermatol 1981" 219-221,

25 "Effect of IL-12 on immune suppression and suppressor cell induction by ultraviolet radiation" 154 : 5114-5120, 1995

26 "Detection of human cytokines in situ using antibody and probe based methods" 185 : 149-175, 1995

27 "Bioactive tumor necrosis factor alpha but not granulocyte-macrophage colony- stimulating factor aorrelates inversely with Langerhans' cell numbers in skin tumors" 75 : 210-216, 1998

28 "Barnetson RS. Langerhans cell migration into ultraviolet light -induced squamous tumors is unrelated to anti-tumor immunity. J Invest Dermatol 1991" 830-834,