Psoriasis is a common skin disorder that is characterized by inflammation, abnormal angiogenesis, and hyperproliferation of the dermis. One of the earliest stages in the development of active skin lesions is the recruitment of proinflammatory cells to the border of the keratinocyte layer. While some pathogenic elements of psoriasis are generalized, the disease entity itself is often localized to extensor surfaces and sites of prior mechanical injury. The mechanisms responsible for this localization are not known. In this proposal we will begin to test the hypothesis that mechanical deformation of keratinocytes is responsible in part for the anatomic localization of psoriatic lesions. Specifically, we propose that mechanical deformation induces a proinflammatory state in keratinocytes that is characterized by the upregulation of chemoattractant proteins. The following specific aims will be addressed. I. To determine if mechanical deformation of cultured keratinocytes results in increased expression of MCP-1 mRNA and protein. II. To determine if mechano-regulation of MCP-1 in keratinocytes occurs via a redox-sensitive mechanism.
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