204: Inducible nitric oxide synthase is upregulated by IL-23/IL-17A axis in inflammatory bowel disease: A study in Algerian patients

Inflammatory bowel diseases (IBDs) are chronic inflammatory diseases of the gastrointestinal tract, which are clinically present as one of two disorders, Crohn’s disease (CD) or ulcerative colitis (UC). The aim of our work was to study the involvement of Th17 subset in bowel disease pathogenesis by nitric oxide (NO) pathway in Algerian patients with IBD. We investigated the correlation between proinflammatory cytokines (IL17, IL23 and IL-6) and NO production in two groups of patients. We analyzed the expression of mRNAs encoding Th17 cytokines, cytokines receptors and NO synthase 2 (NOS2) in plasma of patients. In the same way, the expression of p-STAT3 and NOS2 was measured. We also studied NO modulation by proinflammatory cytokines (IL-17A, IL-6, TNF-α or IL-1β) in presence or absence of All Trans retinoic acid (At RA) in PBMC, monocytes and in colonic mucosa cultures. Analysis of cytokines, cytokines receptors and NOS2 transcripts revealed that levels of mRNA transcripts of the indicated genes are elevated in all IBD groups. Our study shows a significant positive correlation between NO and IL-17A, IL-23, IL-6 levels in plasma of IBD patients. Interestingly, the correlation is significantly higher in patients with active CD. Our study show that both p-STAT3 and iNOS expression were upregulated in PBMCs and colonic mucosa, especially in patients with active Crohn disease.