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Estrogen Downregulates miR-21 Expression and Induces Inflammatory Infiltration of Macrophages in Polymyositis: Role of CXCL10

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Abstract

This study was aimed to explore the role of estrogen in inducing inflammatory infiltration of macrophages in polymyositis (PM) through downregulation of miR-21, which could further inhibit the expression of C-X-C motif chemokine 10 (CXCL10). Biopsies were collected from 20 PM patients before and after treatment of glucocorticoid. Additionally, peritoneal macrophages were isolated from male SD model rats (n = 40). Creatine kinase (CK) and CXCL10 and nuclear factor-kappa (NF-κB) expressions were tested using immunosorbent and immunocytochemical assays. We also conducted transwell assay to observe invasive abilities of cells; RT-PCR and western blot were intended to semi-quantify miR-21 and CXCL10 expressions in vitro and in vivo. Compared with the control group, serum creatine kinase (S-CK) was upregulated in PM subjects, but its content decreased after treatment of immunosuppressive substances (e.g., glucocorticoids). Moreover, hormone treatment can significantly increase miR-21 expressions in PM patients (P < 0.05). However, CXCL10 expressions had an opposite tendency compared to miR-21expressions. Results drawn from rat model were consistent with those discovered in PM patients. Moreover, miR-21 transfection could significantly decrease the relative luciferase activity when it was integrated with CXCL10 3′-untranslated region (3′-UTR) in macrophage. Estrogen treatment can also upregulate the expression of NF-κB in macrophage nucleus. Nonetheless, the upregulated tendency was inhibited by either miR-21 mimics or anti-CXCL10 mAb (P < 0.05). Both macrophage migration and CXCL10 expressions were significantly decreased after applying miR-21 treatments compared with the control group, yet estrogen could enhance macrophage migration and increase CXCL10 expressions (P < 0.05). Immune inhibitors such as glucocorticoids can significantly downregulate miR-21 and upregulate CXCL10, ultimately eliciting the inflammatory infiltration of macrophage.

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Acknowledgments

This study was supported by projects of medical and health technology development program in Zhejiang province (No. 2014kya198).

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  1. Department of Neurological Internal Medicine, Ningbo No.2 Hospital, No.42 Yongfeng North Road, Haishu District, Ningbo, Zhejiang Province, 315000, People’s Republic of China

    Wang Yan, Caijing Chen & Huimin Chen

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Correspondence to Huimin Chen.

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Yan, W., Chen, C. & Chen, H. Estrogen Downregulates miR-21 Expression and Induces Inflammatory Infiltration of Macrophages in Polymyositis: Role of CXCL10. Mol Neurobiol 54, 1631–1641 (2017). https://doi.org/10.1007/s12035-016-9769-6

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