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-1β 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-κB signalling pathway in cervical cancer cells occurred quickly after poly(I:C) treatment. Moreover, the NF-κB 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.

• Authors: Xin Liu, Lihua Meng, Ling Chen, Ying Liang, Bingyu Wang, Qianqian Shao, Huayang Wang, Xingsheng Yang
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 24 Issue 3 Pg. 2284-2293 (02 2020) ISSN: 1582-4934 [Electronic] England
• PMID: 31943744 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• Cytokines
• IL6 protein, human
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• Poly I-C

Topics

• Cell Line
• Cell Line, Tumor
• Cytokines (metabolism)
• Female
• HeLa Cells
• Humans
• Interleukin-1beta (metabolism)
• Interleukin-6 (metabolism)
• Macrophages (drug effects, metabolism)
• NF-kappa B (metabolism)
• Poly I-C (pharmacology)
• Signal Transduction (drug effects)
• THP-1 Cells
• Tumor Microenvironment (drug effects)
• Up-Regulation (drug effects)
• Uterine Cervical Neoplasms (drug therapy, metabolism)