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.
Penton Rol
G
G
Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Polentarutti
N
N
Sironi
M
M
Saccani
S
S
Introna
M
M
Mantovani
A
A
D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II; D017384:Sequence Deletion; D014162:Transfection
D007375:Interleukin-1; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D053574:Receptors, Interleukin-1 Type II