Abnormal expression of oxylipins and related synthesizing/signaling pathways in inflammatory bowel diseases

Prostaglandins Leukot Essent Fatty Acids. 2024 Mar:202:102628. doi: 10.1016/j.plefa.2024.102628. Epub 2024 Jul 1.

Abstract

We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 ​​and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases.

Keywords: Crohn's disease; Fatty acids; Inflammatory bowel diseases; Oxylipins; Specialized pro-resolving mediators; Ulcerative colitis.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Colitis, Ulcerative* / genetics
  • Colitis, Ulcerative* / metabolism
  • Crohn Disease* / genetics
  • Crohn Disease* / metabolism
  • Female
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / metabolism
  • Male
  • Middle Aged
  • Oxylipins* / metabolism
  • Signal Transduction*
  • Young Adult

Substances

  • Oxylipins