Downregulation of endothelin-1 by interleukin-4 during gastric ulcer healing

Biochemical and Biophysical Research Communications
B L SlomianyA Slomiany

Abstract

We investigated the course of events associated with gastric ulcer healing by analyzing mucosal expression of interleukin-4 (IL-4), endothelin-1 (ET-1), tumor necrosis factor-alpha (TNF-alpha), and the activity of constitutive (cNOS) and inducible nitric oxide synthase (NOS-2). Ulcer onset was characterized by a massive epithelial apoptosis associated with a 5.7-fold increase in TNF-alpha, a 17.5-fold increase in NOS-2, and a 3.9-fold increase in ET-1, while mucosal expression of cNOS showed a 7.6-fold drop and IL-4 fell by 37.2%. Healing was accompanied by a rapid raise in IL-4; decrease in apoptosis, TNF-alpha, ET-1, and NOS-2; and a slow recovery in cNOS. The expression of IL-4 returned to control levels by the 7th day of healing and that of ET-1 and TNF-alpha by the 14th day, while apoptotic DNA fragmentation and the activity of NOS-2 remained significantly elevated beyond the 14-day period. The results suggest that a decrease in the mucosal level of IL-4 at ulcer onset may well be a key factor causing dysregulation of ET-1 production, induction of TNF-alpha, and triggering the apoptotic events that affect the efficiency of mucosal repair.

Citations

Mar 31, 2011·World Journal of Gastroenterology : WJG·Noha N NassarDalaal M Abdallah
May 29, 2001·Microscopy Research and Technique·S CalatayudJ V Esplugues
Mar 24, 2004·Inflammopharmacology·B L Slomiany, A Slomiany
Jan 9, 2020·The Korean Journal of Parasitology·Taehee ChangJong-Yil Chai
Oct 13, 2006·Current Opinion in Gastroenterology·P Holzer
Oct 7, 2004·The American Journal of Pathology·Taeko DohiJerry R McGhee
Mar 10, 2000·Biochemical and Biophysical Research Communications·B L Slomiany, A Slomiany

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