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

Of the two known types of specific receptors for interleukin (IL)-1, the function of the type II IL-1 receptor (IL-1R(II)) is still elusive. IL- 1R(II) 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-1R(II), a human keratinocyte cell line has been stably transfected with a cDNA coding for IL-1R(II), and its responsiveness to IL-1 has been compared with that of nontransfected cells. Parental cells express IL-1R(I) and are responsive to low doses of IL-1, whereas transfected cells overexpress IL- 1R(II), both in its membrane and soluble form, and show a dramatically impaired response to IL-1. Selective block of IL-1R(II) restores the ability of transfected keratinocytes to respond to IL-1, indicating that the overexpressed IL-1R(II) 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-1R(II).