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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
Authors:Ying-Ying Li  John W-C Chang  Kun-Yun Yeh
Institution:a Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung and Chang Gung University, College of Medicine, Taiwan
b Graduate Institute of Basic Medicine, Medical College of Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan
c Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kweishan and Chang Gung University, College of Medicine, Taiwan
Abstract: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 (Tyr705) 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.
Keywords:Macrophage  Colon cancer  IL-6  IL-10  MUC1  Migration
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