Merck
  • Home
  • Search Results
  • Downregulation of OCTN2 by cytokines plays an important role in the progression of inflammatory bowel disease.

Downregulation of OCTN2 by cytokines plays an important role in the progression of inflammatory bowel disease.

Biochemical pharmacology (2020-06-25)
Ping Li, Yuqing Wang, Jun Luo, Qingquan Zeng, Miaojuan Wang, Mengru Bai, Hui Zhou, Jinhai Wang, Huidi Jiang
ABSTRACT

Inflammatory bowel diseases (IBD) are characterized by chronic relapsing disorders of the gastrointestinal tract. OCTN2 (SLC22A5) and its substrate l-carnitine (l-Car) play crucial roles in maintaining normal intestinal function. An aim of this study was to delineate the expression alteration of OCTN2 in IBD and its underlying mechanism. We also investigated the impact of OCTN2 on IBD progression and the possibility of improving IBD through OCTN2 regulation. Our results showed decreased OCTN2 expression levels and l-Car content in inflamed colon tissues of IBD patients and mice, which negatively correlated with the degree of colonic inflammation in IBD mice. Mixed proinflammatory cytokines TNF-α, IL-1β and IFNγ downregulated the expression of OCTN2 and subsequently reduced the l-Car content through PPARγ/RXRα pathways in FHC cells. OCTN2 silencing reduced the proliferation rate of the colon cells, whereas OCTN2 overexpression increased the proliferation rate. Furthermore, the ability of PPARγ agonist, luteolin, to increase OCTN2 expression resulted in the alleviation of colonic inflammatory responses. In conclusion, OCTN2 was downregulated in IBD by proinflammatory cytokines via the PPARγ/RXRα pathways, which reduced l-Car concentration and subsequently induced IBD deterioration. Upregulation of OCTN2 by the PPARγ agonist alleviated colonic inflammation. Our findings suggest that, OCTN2 may serve as a therapeutic target for IBD therapy.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
MPP+ iodide, ≥98% (HPLC), powder