Effects of interferons on the production of interleukin-6 and interleukin-8 in human keratinocytes.
Interferons (IFNs) originally described for antiviral activity have been reported to have pleiotropic effects, including the ability to induce interleukin-6 (IL-6) and IL-8 production in several cell types. IL-6 and IL-8 are proinflammatory cytokines and are known to be produced by a wide variety of cells, including human keratinocytes. In the present study, we sought to examine the effects of IFNs on IL-6 and IL-8 production from human keratinocytes. IFN-gamma (10-50 ng/ml) induced IL-6 and IL-8 production dose dependently, but no induction of IL-6 or IL-8 was observed with either IFN-alpha or IFN-beta. Because cytokines often work in a cascade fashion and keratinocytes are a source of primary cytokines, IL-1 alpha, and tumor necrosis factor-alpha (TNF-alpha), we examined whether combined treatment with IFN-gamma and these primary cytokines, IL-1 alpha and TNF-alpha, had a synergistic effect on the production of IL-6 and IL-8. Combined treatment with IFN-gamma and IL-1 alpha induced 6-fold to 7-fold higher levels of IL-6 than IL-1 alpha alone. Combined treatment with IFN-gamma and TNF-alpha induced 11-fold to 12-fold higher levels of IL-6 than TNF-alpha alone. The same treatment induced 3-fold to 4-fold higher levels of IL-8 in both cases. These results suggest that IFN-gamma is a positive regulator for the production of IL-6 and IL-8 from human keratinocytes and likely has an augmentative effect on skin inflammation.
Fujisawa
H
H
Division of Dermatology, Sunnybrook Health Science Centre, University of Toronto, Canada.
Wang
B
B
Sauder
D N
DN
Kondo
S
S
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000235:genetics
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D007372:Interferons