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  • Title: Estrogen Downregulates miR-21 Expression and Induces Inflammatory Infiltration of Macrophages in Polymyositis: Role of CXCL10.
    Author: Yan W, Chen C, Chen H.
    Journal: Mol Neurobiol; 2017 Apr; 54(3):1631-1641. PubMed ID: 26873848.
    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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