Gene transfer-mediated expression of physiological numbers of the type II decoy receptor in a myelomonocytic cellular context dampens the response to interleukin-1.

Available information suggests that the type II IL-1 receptor (RII) is a nonsignaling molecule which acts as a decoy for IL-1. The decoy function model for RII was supported by gene transfer experiments in fibroblasts and keratinocytes. Therefore, inhibition of IL-1 responsiveness after decoy RII gene transfer could reflect a non-physiological cellular context and receptor number. In the present study, constructs encoding RII or a cytoplasmic deletion mutant (delta 372-398) were transfected into U937 cells which express only low levels of RI detectable by RT-PCR. Gene transfer resulted in receptor numbers (approximately equal to 10(3)/cell) of the same order of magnitude as that found in normal myelomonocytic cells. Transfer of RII or a cytoplasmic deletion mutant into U937 did not increase responsiveness to IL-1, as assessed by IL-8 expression and production; it actually considerably dampened it. These results are consistent with the view that in a myelomonocytic cellular context, RII does not contribute to signaling and represents a unique pathway of negative regulation of the IL-1 system.