The roles of keratinocyte-derived cytokines in the epidermis and their possible responses to UVA-irradiation.

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. In this report, the effects of KC-derived cytokines on various components in the skin are briefly summarized. We further demonstrate that ultraviolet (UV) light has a distinct effect on the production and secretion of cytokines from KC, depending upon its wavelength. Although some KC-derived cytokines were induced both by UVA and by UVB, suggesting augmentative effects of UVA on UVB-induced cutaneous responses such as sunburn and suntan, other cytokines, including IL-10 and IL-12, were found to be differentially regulated by UVA and UVB. UVA (less than 20 kJ per m2) was found to induce IL-12 but not IL-10 in normal human KC. Our results suggest an antagonistic effect of UVA against UVB, indicating the contribution of UV irradiation to the balance between Th1 and Th2 cytokines in the in situ skin.