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IL-6 expression promoted by Poly(I:C) in cervical cancer cells regulates cytokine expression and recruitment of macrophages.

ABSTRACT: Poly(I:C) is a promising adjuvant for cancer treatment vaccines to enhance the host anti-tumour immune response. However, the roles of poly(I:C) in the cervical cancer microenvironment and local immune reactions are not well understood. In this study, we investigated the roles of poly(I:C) in the cervical cancer. We analysed the cytokine transcription and secretion of cervical cancer cell lines and THP-1-derived macrophages after poly(I:C) treatment, respectively. These results revealed that IL-6 was significantly up-regulated, and this up-regulation was partly dose dependent. poly(I:C)-stimulated supernatant of cervical cancer cells promoted M1-type cytokine IL-1? and IL-6 expression of THP-1-derived macrophages, but inhibited the expression of M2-type cytokine, IL-10 and CCL22. The recruitment of THP-1-derived macrophages by poly(I:C)-stimulated cervical cancer cell supernatant was also enhanced. Inhibition of IL-6 expression in cervical cancer cells by siRNA transfection almost completely reversed the effects of poly(I:C) treatment. Finally, we found that phosphorylation of the NF-?B signalling pathway in cervical cancer cells occurred quickly after poly(I:C) treatment. Moreover, the NF-?B signalling pathway inhibitor PDTC significantly inhibited poly(I:C)-induced IL-6 expression. Taken together, these results suggest that poly(I:C) might regulate the effects of cervical cancer cells on tumour-infiltrated macrophages, and subsequently promote a pro-inflammatory tumour microenvironment.

SUBMITTER: Liu X

PROVIDER: S-EPMC7011141 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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IL-6 expression promoted by Poly(I:C) in cervical cancer cells regulates cytokine expression and recruitment of macrophages.

Liu Xin X Meng Lihua L Chen Ling L Liang Ying Y Wang Bingyu B Shao Qianqian Q Wang Huayang H Yang Xingsheng X

Journal of cellular and molecular medicine 20200114 3

Poly(I:C) is a promising adjuvant for cancer treatment vaccines to enhance the host anti-tumour immune response. However, the roles of poly(I:C) in the cervical cancer microenvironment and local immune reactions are not well understood. In this study, we investigated the roles of poly(I:C) in the cervical cancer. We analysed the cytokine transcription and secretion of cervical cancer cell lines and THP-1-derived macrophages after poly(I:C) treatment, respectively. These results revealed that IL- ...[more]

PMID: 31943744

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Project description:BackgroundAlpha-momorcharin (α-MMC) is a natural medicine derived from bitter melon and has been found to exert immunomodulatory effects. Our previous study indicated that α-MMC can regulate cytokine release from monocytes, but it remains unknown about its regulatory effect on different types of cytokines, such as inflammatory cytokines or anti-inflammatory cytokines.MethodsLPS-induced M1-type macrophages model and IL-4-induced M2-type macrophages model were established, and the expression of proinflammatory cytokines and anti-inflammatory cytokines were assessed by ELISA after α-MMC was administered. Then, a LPS-induced acute pneumonia mouse model was established, the proinflammatory cytokines levels and inflammatory lesions in lung tissues were examined by ELISA or H&E staining. Furthermore, omics screening analysis and Western blotting verification were performed on TLR4 and JAK1-STAT6 signalling pathway-related proteins to elucidate the regulatory mechanism of α-MMC in those M1 macrophages and M2 macrophages.ResultsAt a noncytotoxic dose of 0.3 μg/mL, α-MMC significantly inhibited the LPS-induced expression of inflammatory cytokines, such as TNF-α, IL-1β, IL-6, IL-8, MIP-1α and MCP-1, by M1 macrophages in a time-dependent manner, but α-MMC did not inhibit the IL-4-induced synthesis of anti-inflammatory cytokines, such as IL-10, IL-1RA, EGF, VEGF, TGF-β and CCL22, by M2 macrophages. Moreover, α-MMC also inhibited inflammatory cytokine expression in an LPS-induced acute pneumonia mouse model and alleviated inflammation in lung tissues. Furthermore, omics screening and Western blotting analysis confirmed that α-MMC inhibited TAK1/p-TAK1 and subsequently blocked the downstream MAPK and NF-κB pathways, thus inhibiting the LPS-induced inflammatory cytokine expression.ConclusionOur results reveal that α-MMC inhibits proinflammatory cytokine expression by M1 macrophages but not anti-inflammatory cytokine expression by M2 macrophages. The efficacy of α-MMC in selectively inhibiting proinflammatory cytokine expression renders it particularly suitable for the treatment of severe inflammation and autoimmune diseases characterized by cytokine storms.

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IL-6 expression promoted by Poly(I:C) in cervical cancer cells regulates cytokine expression and recruitment of macrophages.

Publications

IL-6 expression promoted by Poly(I:C) in cervical cancer cells regulates cytokine expression and recruitment of macrophages.

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