IL-6 and IFN-gamma regulation of IL-10 production by human colon carcinoma cells.
IL-10 has been shown to play a crucial role in immunosuppression in cancer patients. We explored the regulation of IL-10 production by TNF-alpha, IL-1 beta, IL-6, IL-8, and IFN-gamma in human colon carcinoma COLO205 cells. Northern analysis revealed a marked expression of IL-10 mRNA after stimulation by IL-6, and a marginal but significant expression by TNF-alpha, IL-1 beta or IFN-gamma. No IL-10 mRNA expression was observed when cells were untreated or incubated with IL-8. IL-10 in the culture supernatants showed good agreement with mRNA expression. In addition, IFN-gamma dose-dependently inhibited this IL-6-induced production of IL-10. MTT assay revealed that low dose IFN-gamma (1-10 ng/ml) had no effect on growth of COLO205 cells, but that high dose IFN-gamma (>100 ng/ml) significantly inhibited their proliferation. Northern analysis of COLO205 cells pretreated with IFN-gamma demonstrated that the IL-6R alpha chain was down-regulated. These results suggest that, in certain colon carcinoma cells, tumor-derived IL-10 production is directly regulated by systemic or local production of pro-inflammatory cytokines, such as IL-6 and IFN-gamma.
Suzuki
S
S
Department of Surgery II, School of Medicine, Kumamoto University, Kumamoto 860-8556, Japan.
Mita
S
S
Kamohara
H
H
Sakamoto
K
K
Ishiko
T
T
Ogawa
M
M
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D015850:Interleukin-6; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma