Neutralization of interleukin (IL)-10 released by monocytes/macrophages enhances the up-regulatory effect of monocyte/macrophage-derived IL-6 on expressions of IL-6 and MUC1, and migration in HT-29 colon cancer cells.
The interactions between monocyte-derived IL-6 and IL-10 in colon cancer are unknown. We continued previous work that showed monocyte/macrophage-derived IL-6 induces IL-6 and MUC1 expression in HT-29 cancer cells, and evaluated if IL-10 present in monocyte/macrophage is involved in this IL-6-mediated effect. We treated HT-29 cells with monocyte/macrophage supernatant following neutralization of monocyte/macrophage-released IL-10. Neutralization markedly enhanced monocyte/macrophage-derived IL-6 effects on HT-29 cells including IL-6 and MUC1 production and cell migration. Double blocking of IL-6 and IL-10 in monocyte/macrophage supernatants abolished this enhancement. Western blot analysis of STAT3 phosphorylation showed that this augmented response in HT-29 cells following IL-10 neutralization is probably mediated through enhanced IL-6-induced phosphorylation (Tyr(705)) of STAT3 proteins. Therefore, monocytes/macrophages have the capacity to release the functionally associated cytokines IL-6 and IL-10 whose interactions can account for the pathogenesis and progression of colon cancer.
Li
Ying-Ying
YY
Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Taiwan.
Chang
John W-C
JW
Hsieh
Ling-Ling
LL
Yeh
Kun-Yun
KY
D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology / Q000473:pathology; D017077:Culture Media, Conditioned; D019073:HT29 Cells; D006801:Humans; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D018396:Mucin-1 / Q000096:biosynthesis / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D017077:Culture Media, Conditioned; D015850:Interleukin-6; C060192:MUC1 protein, human; D018396:Mucin-1; D050796:STAT3 Transcription Factor; D016753:Interleukin-10