PMID: 9159157May 27, 1997Paper

Keratinocyte expression of the type 2 interleukin 1 receptor mediates local and specific inhibition of interleukin 1-mediated inflammation

Proceedings of the National Academy of Sciences of the United States of America
T RauschmayrT S Kupper

Abstract

Epidermal keratinocytes can express two types of interleukin 1 (IL-1) receptors: IL-1R1, which is active in signal transduction, and the less well characterized IL-1R2, which is incapable of transducing a signal and can be shed from cells. The binding of IL-1 in solution by IL-1R2 has been demonstrated, and it has been proposed to inhibit IL-1-mediated responses through this mechanism. We and others have reported that keratinocytes can be induced to express IL-1R2 both in vitro and in vivo, often under conditions that also favor IL-1 gene expression. We hypothesized that production of IL-1R2 by keratinocytes would be an efficient means to achieve local inhibition of IL-1-mediated responses without systemic consequences. To test this hypothesis, we have generated transgenic mice that constitutively express IL-1R2 on basal keratinocytes. Keratinocytes cultured from these animals shed the soluble form of the receptor into culture supernatants, and IL-1-inducible production of granulocyte/macrophage colony-stimulating factor was markedly inhibited. In vivo, acute cutaneous vascular leakage, as well as chronic inflammation induced by a well characterized IL-1-dependent stimulus, was significantly inhibited in IL-1R2 transgenic anima...Continue Reading

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