The objective of this proposal will be to address unresolved issues concerning the immunosuppressive effects of ultraviolet B (UVB) radiation human skin. We plan to test the hypothesis that UVB radiation mediates its effects on human cutaneous immune function, at least in part, by inhibiting the capacity of epidermal tissue to activate populations of T lymphocytes necessary for the development of cell-mediated immune responses. We will first compare the accessory function of unfractionated epidermal cell suspensions and purified Langerhans cells following in vitro exposure to various doses of UVB radiation in in vitro T lymphocyte proliferation assays. Different antigenic stimuli will be employed each of which provides complementary information regarding the mechanisms by which accessory cells activate T lymphocytes. In other studies, epidermal cell suspensions and purified Langerhans cells will be pretreated with cytokines or will be precultured before UVB exposure in an attempt to protect epidermal accessory function from the adverse effects of UVB radiation. Efforts will be made to assess the impact of UVB radiation on epidermal accessory signals, such as adhesion molecule expression and antigen processing, that are required for T cell activation. Studies will be conducted to define the molecular mechanisms by which ultraviolet radiation inhibits ICAM-1 expression. Finally, we will correlate the adverse effects of in vivo UVB radiation exposure on epidermal accessory function with inhibition in the development of contact hypersensitivity that occurs when attempts are made to immunize individuals to DNCB by applying it through UVB-irradiation skin. Knowledge obtained from these studies may help to define the effect of UVB exposure on cutaneous immunological processes and enhance our understanding of the role that this environmental agent plays in the pathogenesis of human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR032593-08
Application #
3156350
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-08-01
Project End
1996-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
8
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Haeffner, A C; Zepter, K; Elmets, C A et al. (1997) Analysis of tumor-infiltrating lymphocytes in cutaneous squamous cell carcinoma. Arch Dermatol 133:585-90
De Luca, D J; Trefzer, U; Tubesing, K A et al. (1997) ICAM-1 mRNA levels and relative transcription rates are decreased by UV irradiation of monocytes. Photochem Photobiol 65:609-15
Haffner, A C; Zepter, K; Elmets, C A (1996) Major histocompatibility complex class I molecule serves as a ligand for presentation of the superantigen staphylococcal enterotoxin B to T cells. Proc Natl Acad Sci U S A 93:3037-42
Boehm, K D; Yun, J K; Strohl, K P et al. (1996) In situ changes in the relative abundance of human epidermal cytokine messenger RNA levels following exposure to the poison ivy/oak contact allergen urushiol. Exp Dermatol 5:150-60
Elmets, C A; Anderson, C Y (1996) Sunscreens and photocarcinogenesis: an objective assessment. Photochem Photobiol 63:435-40
Katiyar, S K; Elmets, C A; Agarwal, R et al. (1995) Protection against ultraviolet-B radiation-induced local and systemic suppression of contact hypersensitivity and edema responses in C3H/HeN mice by green tea polyphenols. Photochem Photobiol 62:855-61
Gould, J W; Mercurio, M G; Elmets, C A (1995) Cutaneous photosensitivity diseases induced by exogenous agents. J Am Acad Dermatol 33:551-73;quiz 574-6
Klein, L R; Elmets, C A; Callen, J P (1995) Photoexacerbation of cutaneous lupus erythematosus due to ultraviolet A emissions from a photocopier. Arthritis Rheum 38:1152-6
Boehm, K D; Yun, J K; Strohl, K P et al. (1995) Messenger RNAs for the multifunctional cytokines interleukin-1 alpha, interleukin-1 beta and tumor necrosis factor-alpha are present in adnexal tissues and in dermis of normal human skin. Exp Dermatol 4:335-41
Zepter, K; Haffner, A C; Trefzer, U et al. (1995) Reduced growth factor requirements and accelerated cell-cycle kinetics in adult human melanocytes transformed with SV40 large T antigen. J Invest Dermatol 104:755-62

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