当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE期刊下所有文献 > Tumor necrosis factor-α acts reciprocally with solute carrier family 26, member 3, (downregulated-in-adenoma) and reduces its expression, leading to intestinal inflammation.

Tumor necrosis factor-α acts reciprocally with solute carrier family 26, member 3, (downregulated-in-adenoma) and reduces its expression, leading to intestinal inflammation.

Abstract：

:Solute carrier family 26, member 3 (Slc26a3), also termed downregulated-in-adenoma (DRA) is a member of the Slc26 family of anion transporters and is mutated in congenital chloride diarrhea. Our previous study demonstrated that DRA deficiency is associated with severely reduced colonic HCO3‑ secretion, a loss of colonic fluid absorption, a lack of a firmly adherent mucus layer and a severely reduced colonic mucosal resistance to dextran sodium sulfate (DSS) damage. However, the direct effect of mediators that trigger intestinal inflammatory factors on DRA has not been fully investigated. Tumor necrosis factor (TNF)‑α is a central mediator of intestinal inflammation in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease. However, to the best of our knowledge, whether TNF‑α acts reciprocally with DRA leading to the development of gut inflammation in IBD has not been reported. The present study identified that the expression level of DRA was reduced in active UC patients and DSS‑induced colitis mice with high expression levels of TNF‑α identified in the peripheral blood serum. In addition, TNF‑α may affect the expression level of DRA in human colonic Caco2BBE cells in a dose‑dependent manner, including in DRA overexpressed Caco2BBE cells. Furthermore, knockdown of TNF‑α in Caco2BBE cells led to a higher expression level of DRA and a markedly reduced secretion of TNF‑α in the culture media. In addition, knockdown of DRA in Caco2BBE cells led to a higher secretion of TNF‑α in the culture media compared with the control cells, which could be reversed by overexpression of DRA. Overall, these results indicate that TNF‑α may act reciprocally with DRA, leading to the development of intestinal inflammation. Based on the pivotal position of TNF‑α in IBD, DRA is hypothesized to have therapeutic potential against colitis serving as an important target.

journal_name

Int J Mol Med

journal_title

International journal of molecular medicine

authors

Ding X,Li D,Li M,Tian D,Yu H,Yu Q

doi

10.3892/ijmm.2017.3347

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

1224-1232

issue

eissn

1107-3756

issn

1791-244X

journal_volume

pub_type

杂志文章

在线工具

Tumor necrosis factor-α acts reciprocally with solute carrier family 26, member 3, (downregulated-in-adenoma) and reduces its expression, leading to intestinal inflammation.