MiR-155 modulates the inflammatory phenotype of intestinal myofibroblasts by targeting SOCS1 in ulcerative colitis

Abstract

Abnormal levels of microRNA (miR)-155, which regulate inflammation and immune responses, have been demonstrated in the colonic mucosa of patients with inflammatory bowel diseases (IBD), although its role in disease pathophysiology is unknown. We investigated the role of miR-155 in the acquisition and maintenance of an activated phenotype by intestinal myofibroblasts (IMF), a key cell population contributing to mucosal damage in IBD. IMF were isolated from colonic biopsies of healthy controls, ulcerative colitis (UC) and Crohn's disease (CD) patients. MiR-155 in IMF was quantified by quantitative reverse transcription-PCR in basal condition and following exposure to TNF-α, interleukin (IL)-1β, lipopolysaccharide (LPS) or TGF-β1. The effects of miR-155 mimic or inhibitor transfection on cytokine release and suppressor of cytokine signaling 1 (SOCS1) expression were assessed by enzyme-linked immunosorbent assay and western blot, respectively. Regulation of the target gene SOCS1 expression by miR-155 was assessed using luciferase reporter construct. We found that miR-155 was significantly upregulated in UC as compared with control- and CD-derived IMF. Moreover, TNF-α and LPS, but not TGF-β1 and IL-1β, significantly increased miR-155 expression in IMF. Ectopic expression of miR-155 in control IMF augmented cytokines release, whereas it downregulated SOCS1 expression. MiR-155 knockdown in UC-IMF reduced cytokine production and enhanced SOCS1 expression. Luciferase reporter assay demonstrated that miR-155 directly targets SOCS1. Moreover, silencing of SOCS1 in control IMF significantly increased IL-6 and IL-8 release. In all, our data suggest that inflammatory mediators induce miR-155 expression in IMF of patients with UC. By downregulating the expression of SOCS1, miR-155 wires IMF inflammatory phenotype.

SOCS1 is a negative regulator of metabolic reprogramming during sepsis

“…We speculate that these conflicting results could be due to differences in sepsis severity and/or the time points studied. Indeed, alterations in SOCS1 expression have been associated with disease severity for several inflammatory disorders (48,(56)(57)(58). To further determine whether SOCS1 expression is increased in patients with sepsis, we employed transcriptomic analysis and found elevated levels of SOCS1 in peripheral blood cells from septic pediatric patients as compared with healthy subjects.…”

S100A8 facilitates the migration of colorectal cancer cells through regulating macrophages in the inflammatory microenvironment

“…In addition, we found that aberrant miR-155 expression controlled gene expression of IL-1β and TNF-α and secretions of IL-1β and TNF-α in macrophages. It is possible that miR-155 post-transcriptionally modulates the expression of multiple target genes, including suppressor of cytokine signaling 1 (SoCS1) (16), forkhead box o3 (FoXo3a) (50), transcription factor CCAAT/enhancer binding protein β (C/EBPβ) (51), which were proven to regulate the expression of various inflammatory cytokines. Moreover, some studies have reported that TNF-α can significantly increase miR-155 expression in macrophages (52).…”

“…miR-155, an oncogenic miRNA, is identified as a link between inflammation and cancer (14). Previous studies have found that miR-155 expression is induced by proinflammatory mediators, such as TnF-α and LPS (15), and overexpression of miR-155 has been found to elevate inflammatory cytokine production in intestinal myofibroblasts (16) and monocyte/macrophages (17,18). In addition, some studies indicate that the promoter region of pri-miR-155 contains putative NF-κB-binding sites (19,20) and miR-155 upregulation and subsequent molecular events are associated with inflammatory processes such as activation of nF-κB (21,22).…”

The Modern View of the Pathogenesis and Laboratory Diagnostics of Ulcerative Colitis (Literature Review)

“…В перспективе ученые планируют использовать этот факт в созда-нии иммуноподавляющей мишени терапии. Изме-нение уровня miR-155, которое регулирует воспали-тельные и иммунные реакции, было продемонстри-ровано в биоптатах слизистой оболочки больных ЯК [41]. В исследование были включены больные ЯК (n=8) и БК (n=8).…”