Contents lists available at ScienceDirect International Immunopharmacology journal homepage: www.elsevier.com/locate/intimp Immunomodulatory effects of M2000 (β-D-Mannuronic acid) on TNF-α, IL- 17 and FOXP3 gene expression in patients with inflammatory bowel disease Hussaini Alhassan Mohammed a,b , Ali Akbar Saboor-Yaraghi a , Homayoun Vahedi c , Mir Saeed Yekaninejad d , Ghodratollah Panahi e , Gholamreza Hemmasi f , Mostafa Lakzaei e , Abbas Mirshafiey a,⁎ a Department of Immunology, School of Public Health, Tehran University of Medical Sciences, International Campus, TUMS-, IC, Tehran, Iran b Department of Immunology, Faculty of Medical Laboratory Sciences, Usmanu Danfodiyo University, Sokoto, Nigeria c Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran d Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran e Department of Medical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran f Department of Internal Medicine and Gastroenterology, Iran University of Medical Sciences, Tehran, Iran ARTICLE INFO Keywords: β-D Mannuronic acid Ulcerative colitis Crohn's disease Immunosuppression Immunomodulation ABSTRACT Introduction: Inflammatory 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 gastro- intestinal 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/objective: This 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. Methodology: Ten (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 in- cubated 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. Results: Our findings showed a significant down-regulation of TNF-α and IL-17 gene expression, while the ex- pression of FOXP3 gene was significantly up-regulated. Conclusion: This result has indicated that β-D Mannuronic acid (M2000) have immunoregulatory and anti-in- flammatory effects on these cytokines that are pivotal in the pathogenesis of IBD. 1. Introduction The inflammatory bowel diseases (IBD) are a group of idiopathic, chronic, relapsing inflammatory disorders whose etiologic origins are yet to be understood, but current investigations have attributed the emergence of this disease to genetic susceptibility, immune dysregula- tions, environmental factors and/or bacterial infections [1,2]. IBD is of two subtypes, Ulcerative colitis (UC) and Crohn's disease (CD). The UC is a T-helper-2-like (Th2) inflammatory disorder, the morphological changes are restricted to the colon, more-so; the rectum is involved in about 95% of patients [3]. Crohn's disease (CD) is a T-helper-1 medi- ated (Th1), inflammatory condition which may extend from the oesophagus to the anus, but the ileocecal region and terminal ileum are the most commonly affected areas [4]. Inflammation in CD is usually transmural with a resultant of fistula formation. In most cases, the af- fected parts are bridged by intervening normal bowel. Immunological abnormality is demonstrated in IBD patients and imbalance between pro-inflammatory and anti-inflammatory cytokines play an important role in the initiation and regulation of the immune responses [5,6]. Tumor necrosis factor alpha (TNF-α) is a master cytokine in the pathogenesis of IBD [7]. The source of TNF-α in IBD is partly the innate immune cells, such as macrophages or monocytes, and also differ- entiated Th1 cells [8]. The serum levels of TNF-α correlate with the clinical activity of UC and CD [9]. It's orchestrating role in colonic http://dx.doi.org/10.1016/j.intimp.2017.08.011 Received 5 July 2017; Received in revised form 5 August 2017; Accepted 14 August 2017 ⁎ Corresponding author at: Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran E-mail address: mirshafiey@tums.ac.ir (A. Mirshafiey). International Immunopharmacology 51 (2017) 107–113 1567-5769/ © 2017 Published by Elsevier B.V. MARK