2015
DOI: 10.1371/journal.pone.0135858
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Metformin Ameliorates Inflammatory Bowel Disease by Suppression of the STAT3 Signaling Pathway and Regulation of the between Th17/Treg Balance

Abstract: ObjectiveMetformin is used to treat type 2 diabetes. We sought to determine whether metformin reduces inflammation, by regulating p-signal transducer and activator of transcription 3 (STAT3) expression and T-helper 17 (Th17) cell proliferation, in a mouse model of inflammatory bowel disease (IBD).MethodsIBD mice were administered metformin for 16 days and their tissues were analyzed. AMP-activated protein kinase (AMPK), the mammalian target of rapamycin (mTOR), p-STAT3 and p-STAT5 in the spleen and lymph nodes… Show more

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Cited by 160 publications
(153 citation statements)
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“…This represents a close, fundamental relationship between the two cell types and further suggests shared developmental pathways during the progression of immune-mediated inflammatory conditions (22, 37). This is supported by data suggesting that the balance of Th17/Treg plays a role in the regulation of intestinal inflammation in IBD (3840). A balance between the effector and regulatory functions (respectively mediated by Th17 cells and Tregs) is particularly important in the GI tract as it represents a critical barrier between the internal and external environments.…”
Section: Th17/treg Balance In Ibdssupporting
confidence: 56%
“…This represents a close, fundamental relationship between the two cell types and further suggests shared developmental pathways during the progression of immune-mediated inflammatory conditions (22, 37). This is supported by data suggesting that the balance of Th17/Treg plays a role in the regulation of intestinal inflammation in IBD (3840). A balance between the effector and regulatory functions (respectively mediated by Th17 cells and Tregs) is particularly important in the GI tract as it represents a critical barrier between the internal and external environments.…”
Section: Th17/treg Balance In Ibdssupporting
confidence: 56%
“…In addition, metformin regulates the balance between Th17 and T reg cells [49]. Treatment of metformin helps the differentiation of T reg cells while down-regulating proinflammatory Th17 cells, which subsequently ameliorates inflammation in inflamed bowel [49]. In current study, metformin decreased IFN-γ and TNF-α contents, and reduced the recruitment of pro-inflammatory macrophages, suggesting that metformin/AMPK could ameliorate inflammation and associated epithelial barrier damage.…”
Section: Discussionmentioning
confidence: 64%
“…Metformin is a potent AMPK activator, and AMPK activation helps to induce macrophage polarization into an anti-inflammatory phenotype [48]. In addition, metformin regulates the balance between Th17 and T reg cells [49]. Treatment of metformin helps the differentiation of T reg cells while down-regulating proinflammatory Th17 cells, which subsequently ameliorates inflammation in inflamed bowel [49].…”
Section: Discussionmentioning
confidence: 99%
“…Recent studies in mice and humans reported a wide efficacy of metformin, an AMPK activator classically used for hyperglycaemia and T2D treatment, in the treatment of autoimmune disorders. Treatment with metformin inhibited mTOR phosphorylation and increased FOXP3 expression, positively affecting the Treg/Th17 cell balance in humans with multiple sclerosis and in mice with inflammatory bowel disease (114, 115). Pathways others than mTOR can be relevant as well as pioglitazone (PIO) - a drug used for type 2 diabetes that stimulates peroxisome proliferator-activated receptor (PPAR)-γ - also restored number and function of visceral adipose tissue (VAT) Treg cells (74).…”
Section: Metabolic Targeting Of Treg Cell Number and Function In Pmentioning
confidence: 99%