|Budget Amount *help
¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 2000 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Skin is the largest organ, covering the entire body surface. Keratinocytes (KC) are its major component. The KC, by making keratin protein, function as a protective barrier against exogenous stimuli. As KC have been demonstrated to produce various kinds of cytokines, skin plays an important role in immunologic and inflammatory responses of the body. Cytokines affect other cells and organs, mediating cellular growth and differentiation as well as inflammation and immune reactions. Thus, cytokines maintain the cellular and intercellular homeostasis. Dysregulation and abnormal production of cytokines are detected in various skin diseases. Evidence is accumulating to show the significant contribution of cytokines to the pathogenesis or severity of certain diseases. We have found that ultraviolet light affects KC to produce a variety of cytokines, and suggested that they are involved in various pathophysiologic conditions observed in the skin exposed to sunlight including erythema formation
, immune suppression, carcinogenesis and photoaging.
UVR-induced inflammation, sunburn, is mainly induced by UVB, but UVA is known to augment its reaction. In order to find if this augmentative effect of UVA is due to the effect of UVA on KC to induce proinflammatory mediators including cytokines and PGE_2, normal human KC were cultured and irradiated by UVB and UVA either separately or concomitantly. Levels of mRNA for each cytokine were determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method and protein production in cultured supernatants was assayed by enzyme-linked immunosorbent assay (ELISA) or enzyme immunoassay (EIA). UVB (300 J/m^2) induced the expression of IL-6, IL-8, TNF-α, TGF-β1 and GM-CSF mRNA at 24 h after irradiation, while an increase only in IL-6 and IL-8 mRNA levels was observed at 24 h after UVA irradiation (10 kJ/m^2). IL-1α, IL-6, IL-8 and PGE_2 production was increased additively by UVB and UVA, but significant levels of TNF-α., TGF-β1 and GM-CSF protein in cultured supernatants were detected only after UVB irradiation. These results indicate that UVB and UVA differentially regulate the expression and production of IL-derived cytokines and UVA is able to induce proinflammatory mediators from KC additively to UVB.Our results explain the mechanism by which UVA augments UVB-induced skin inflammation. IL-12, which is known to restore UVB-induced immune suppression, was induecd by UVA under our experimental condition suggesting that UVA may inhibit Less