title: Estrogen Downregulates miR-21 Expression and Induces Inflammatory Infiltration of Macrophages in Polymyositis: Role of CXCL10.
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.
authors.affiliation: 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.
authors.forename: Wang
authors.initials: W
authors.lastname: Yan
authors.affiliation: 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.
authors.forename: Caijing
authors.initials: C
authors.lastname: Chen
authors.affiliation: 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. chenhuimin233@163.com.
authors.forename: Huimin
authors.initials: H
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000502:physiology*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D017285:Polymyositis / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D004967:Estrogens; C524940:MIRN21 microRNA, human; D035683:MicroRNAs
keywords: CXCL10; Estrogen; Inflammatory infiltration of macrophage; Polymyositis; miR-21