Immunomodulatory effects of M2000 (β-D-Mannuronic acid) on TNF-α, IL-17 and FOXP3 gene expression in patients with inflammatory bowel disease


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Abstract

IntroductionInflammatory bowel diseases (IBD) are immune-mediated disorders that result from an aberrant immunological response to the gut luminal antigen in genetically susceptible patients. IBD is categorized into two serotype, Crohn's diseases (CD) and ulcerative colitis (UC), both subtype are important cause of gastrointestinal diseases. The increasing rate of hospitalization, with the high economic burden experienced by the IBD patients, calls for more concerted research efforts to design a potent and affordable treatment option for the treatment of IBD.Aims/objectiveThis research was designed to test the efficacy and potency of β-D Mannuronic acid (M2000) and assess if it could serve as a better therapeutic option in the treatment of IBD.MethodologyTen (10)ml of blood was aseptically collected into an EDTA container, from 24 IBD patients and 24 normal healthy controls. PBMC was isolated and stimulated with 1 μg/ml of LPS in cell culture plate and incubated for 4 h. The cells were later treated with 10 μg/ml and 50 μg/ml of β-D Mannuronic acid (M2000) and incubated for 24 h at 37 °C under 5% CO2 and 100% humidity. The RNA extractions, cDNA synthesis, and QRT-PCR were performed.ResultsOur findings showed a significant down-regulation of TNF-α and IL-17 gene expression, while the expression of FOXP3 gene was significantly up-regulated.ConclusionThis result has indicated that β-D Mannuronic acid (M2000) have immunoregulatory and anti-inflammatory effects on these cytokines that are pivotal in the pathogenesis of IBD.HighlightsThis research assessed the effects of M2000 in the treatment of IBD.The baseline gene expressions for TNF-α, IL-17 and FOXP3 were 5.2, 4.1 and 0.35 fold respectively.There was a significant downregulations in TNF-α and IL-17, while FOXP3 gene expression was upregulated.These results indicated that M2000 possessed both immunoregulatory and Immunosuppressive effects in IBD pathogenesis.Further research should be undertaken to assess the effects of M2000 under in vivo condition.

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