Cytokines play important roles in the regulation of immune responses by controlling proliferation, differentiation and the effector functions of immune cells. Many cytokines can be secreted by several cell types and have multiple biological functions, depending on the local context in which the cytokine is produced. IL-10 is a key cytokine which contributes to down regulation of cell mediated immune responses in skin. The striking biological properties of Il-10 justify speculation regarding possible clinical use of IL-10. The goal of this proposal is to characterize the regulated expression of IL-10. Murine keratinocytes will be characterized for induction of IL- 10 by UVB. The level of IL-10 regulation will be determined by assessing IL-10 mRNA stability and by nuclear run on experiments. Furthermore, the promoter region for IL-10 will be analyzed for cis- controlling elements using transient transfections. In addition, trans- acting elements will be determined by electrophoretic mobility shift assays and DNAse footprinting experiments. Understanding the molecular mechanisms involved in the regulation of IL-10 induction should provide immunotherapeutic alternatives for modulating the course of cutaenous immune responses.
