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American Journal of Pathology, Vol 147, 1852-1861, Copyright © 1995 by American Society for Investigative Pathology

REGULAR ARTICLES

Transfected type II interleukin-1 receptor impairs responsiveness of human keratinocytes to interleukin-1

P Bossu, U Visconti, P Ruggiero, G Macchia, M Muda, R Bertini, C Bizzarri, A Colagrande, V Sabbatini and G Maurizi
Research Center Dompe SpA, L'Aquila, Italy.

Of the two known types of specific receptors for interleukin (IL)-1, the function of the type II IL-1 receptor (IL-1RII) is still elusive. IL-1RII is allegedly devoid of signaling capacity and is therefore thought to act by trapping and inhibiting IL-1. To directly assess the functional role of IL-1RII, a human keratinocyte cell line has been stably transfected with a cDNA coding for IL-1RII, and its responsiveness to IL-1 has been compared with that of nontransfected cells. Parental cells express IL-1RI and are responsive to low doses of IL-1, whereas transfected cells overexpress IL-1RII, both in its membrane and soluble form, and show a dramatically impaired response to IL-1. Selective block of IL-1RII restores the ability of transfected keratinocytes to respond to IL-1, indicating that the overexpressed IL- 1RII is in fact uniquely responsible for their refractoriness to IL-1. The main mechanism of unresponsiveness in transfected keratinocytes appears to be the capture and neutralization of IL-1 by the soluble form of IL-1RII.

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