Metformin exerts anti‑inflammatory effects on mouse colon smooth muscle cells in�vitro

Abstract

Inflammatory bowel disease (IBD) is a chronic incurable condition characterized by relapsing inflammation of the gut. Intestinal smooth muscle cells (SMCs) are affected structurally and functionally during IBD due to excessive production of different inflammatory mediators. Metformin is a widely used antidiabetic agent known to exert several anti-inflammatory effects in different tissues independently from its hypoglycemic effect. The aim of the present study was to investigate the effect of metformin on expression and secretion of different cytokines and chemokines from mouse colon SMCs (CSMCs) following induction of inflammation with lipopolysaccharide (LPS) . CSMCs from male BALB/c mice were isolated and cultured in Dulbecco's modified Eagle's medium and treated with LPS (1 µg/ml) and 0, 5, 10 or 20 mM metformin for 24 h. Expression and secretion of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), macrophage colony stimulating factor (M-CSF), T cell activation gene-3 (TCA-3) and stromal cell-derived factor-1 (SDF-1) was evaluated by ELISA. LPS-treated CSMCs demonstrated significantly increased expression of TNF-α, IL-1α, M-CSF, TCA-3 and SDF-1 when compared with the control group (P<0.05). Co-treatment with metformin (5 and 10 mM) significantly reduced their expression by ~20-40% when compared with LPS treatment alone (P<0.05). Furthermore, secretion of TNF-α, IL-1α, M-CSF and TCA-3 into the conditioned media was significantly decreased by metformin (5 and 10 mM; P<0.05). In addition, metformin decreased levels of LPS-induced nuclear factor-κB phosphorylation. These data suggest that metformin may provide beneficial anti-inflammatory effects on CSMCs and it may be utilized as an adjunct therapy for patients suffering from IBD.

Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function

“…In addition to its anti-inflammatory effects in VSMCs, metformin inhibits lipopolysaccharide (LPS)-induced NF-kB activation, expression and secretion of cytokines and chemokines (including TNF-a, IL-1a, T cell activation gene-3 [TCA-3], macrophage colony-stimulating factor [M-CSF]) in mouse colonic SMCs (CSMCs) (Al-Dwairi et al, 2018). The anti-inflammatory effect of metformin in CSMCs suggests that it can be used as adjunctive therapy for patients with inflammatory bowel disease (a recurrent inflammation of the intestine and the structure and function of intestinal SMCs are significantly affected) (Al-Dwairi et al, 2018).…”

The Role of Inflammatory Mediators in the Development of Gastrointestinal Motility Disorders

“…Van Assche et al also demonstrated that IL-1 treatment of isolated intestinal smooth muscle cells induces the secretion of IL-6 and this effect was blocked by IL-1 receptor antagonists [81]. More recently, the secretion of TNF-α and IL-1β by colonic smooth muscle cells from BALB/c mice in response to LPS was demonstrated by Al-Dwairi et al [82]. Co-treatment with metformin attenuated the effects of LPS on cytokine secretion in this model.…”

Protection by metformin against severe Covid-19: An in-depth mechanistic analysis

“…During the past years MET effects on inflammation have been the subject of many reports. Indeed, MET decreases cytokine levels in vascular cells [29] , experimental myocarditis [30] , sepsis [31] , gut inflammation [32] , interleukin (IL)-10 deficient mice [33] , lipopolysaccharide (LPS)-stimulated mouse colon cells [34] , metabolic syndrome induced by fructose [35] , PCOS [36] , and animals or patients with diabetes [37] . Interestingly, these effects of MET are independent of its antihyperglycaemic action [38] .…”