Role of intracellular interleukin-1 receptor antagonist in skin carcinogenesis.
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-1alpha 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.
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Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center Science Park-Research Division, Smithville 78957, USA.
Rundhaug
J E
JE
Fischer
S M
SM
D000818:Animals; D015152:Blotting, Northern; D015197:Carcinogenicity Tests / Q000379:methods*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002455:Cell Division; D051546:Cyclooxygenase 2; D005260:Female; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured
C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007527:Isoenzymes; D012795:Sialoglycoproteins; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases