Modulation of pro-inflammatory cytokines in normal and inflamed skin

This thesis describes the expression and modulation of pro-inflammatory cytokines in normal and inflamed skin. During the last few decades it has become clear that the skin comprises a complex network of interacting cells including keratinocytes (KC). dendritic cells (such as Langerhans cells: LC). macrophages. endothelial cells. fibroblasts and T cells. During an infectional or trauma incident. resident and invading cells in skin initiate a complex cascade of events resulting in an inflammatory reaction and ultimately in the elimination of the infectious agent or recovery of the wound. Pro-inflammatory cytokines like members of the interleukin-1 (IL-l) fantily of proteins. tumor necrosis factor-a (TNF-a) and IL-6 play a prominent role in the induction and maintenance of this inflammatory response. When the expression of cytokines in skin is altered. it can result in an inflammatory disease like psoriasis. Thus the regulation of cytokine expression must be tightly orchestrated. The regulation of pro-inflanunatory cytokines in normal and inflamed skin is still incompletely understood. During the study presented in this thesis the modulation and effects of pro-inflanunatory cytokines in skin were investigated. This introduction is focussed on the expression of these pro-inflammatory cytokines. The following paragraphs deal with the architecture of the skin. the interaction and cross talk of the cells residing in it and the expression and regulation of the IL-l family of proteins.

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