Role of intracellular interleukin-1 receptor antagonist in skin carcinogenesis

✍ Scribed by Eunhye La; Joyce E. Rundhaug; Susan M. Fischer

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 148 KB
• Volume: 30
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.1031

✦ Synopsis

Abstract

Interleukin 1 (IL‐1) is a major mediator of inflammation and exerts pleiotropic effects on many systems. To elucidate the role of its endogenous inhibitor, intracellular IL‐1 receptor antagonist (icIL‐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‐1α mRNA levels in these transfected cells. In icIL‐1Ra‐JWF2 cells, however, cyclooxygenase‐2 mRNA levels were dramatically reduced and shown to be transcriptionally regulated by icIL‐1Ra. To determine the effect of icIL‐1Ra on cell proliferation, cell counts were done 24 h after plating equal numbers of cells. Cells from three icIL‐1Ra‐JWF2 clones showed significantly reduced growth rates compared with parental JWF2 cells. We subcutaneously injected five independent clones of icIL‐1Ra‐JWF2 cells into nude mice and measured the tumor doubling time by weekly measurements of tumor volume. IcIL‐1Ra appeared to significantly slow the growth of tumors in vivo. Collectively these observations suggest that IL‐1Ra has antiproliferative effects in murine skin carcinoma cells. © 2001 Wiley‐Liss, Inc.