Inhibition of anthralin-caused skin tumor promotion and interleukin-1 alpha production by potent immunosuppressant FK506.
The effect of FK506, a potent immunosuppressive agent, on 7,12-dimethylbenz[alpha]anthracene-initiated and anthralin-promoted skin tumor formation was examined in CD-1 mice. A topical application of 0.1 mumol FK506 to mouse skin 15 min prior to each anthralin treatment markedly inhibited skin tumor formation. Anthralin stimulated IL-1 alpha production in primary cultured mouse epidermal cells, and the peak IL-1 alpha level was observed at 6 h after the stimulation. Anthralin also stimulated IL-1 alpha release into culture medium. Both production and release of Il-1 alpha were markedly inhibited by FK506 (0.1 or 1 microM). FK506 (1 microM) alone neither affected IL-1 alpha production nor its release. It may be possible that the inhibition of IL-1 alpha production by FK506 is related to its anti-tumor-promoting action.
Yamamoto
S
S
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Jiang
H
H
Kato
R
R
D000287:Administration, Topical; D000818:Animals; D000875:Anthralin / Q000037:antagonists & inhibitors*; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis*; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D016559:Tacrolimus / Q000008:administration & dosage*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007375:Interleukin-1; D000875:Anthralin; D016559:Tacrolimus