Role of intracellular interleukin-1 receptor antagonist in skin carcinogenesis

Interleukin 1 (IL-1) is a major mediator of inflammation and exerts pleiotr opic effects on many systems. To elucidate the role of its endogenous inhib itor, intracellular IL-1 receptor antagonist (iclL-1Ra), in mouse skin, we produced an icIL-1Ra-overexpressing skin carcinoma cell line (icIL-1Ra-JWF2 ). Altered expression of icIL-1Ra did not change IL-1 alpha mRNA levels in these transfected cells. In icIL-1Ra-JWF2 cells, however, cyclooxygenase-2 mRNA levels were dramatically reduced and shown to be transcriptionally reg ulated by icIL-1Ra. To determine the effect of icIL-1Ra on cell proliferati on, cell counts were done 24 h after plating equal numbers of cells. Cells from three icIL-1Ra-JWF2 clones showed significantly reduced growth rates c ompared with parental JWF2 cells. We subcutaneously injected five independe nt clones of icIL-1Ra-JWF2 cells into nude mice and measured the tumor doub ling time by weekly measurements of tumor volume. IcIL-1Ra appeared to sign ificantly slow the growth of tumors in vivo. Collectively these observation s suggest that IL-1Ra has antiproliferative effects in murine skin carcinom a cells. (C) 2000 Wiley-Liss. Inc.