Role of Endothelin-1 and Interleukin-4 in Buccal Mucosal Ulcer Healing: Effect of Chronic Alcohol Ingestion

Abstract

We investigated the effect of chronic alcohol ingestion on buccal mucosal ulcer healing by analyzing the interplay between mucosal expression of tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1), and interleukin-4 (IL-4). Chronic ulceration was induced in rats maintained for 5 weeks on alcohol-containing or control liquid diet. In both groups, the ulcer onset was characterized by a massive increase (6.5–8.9-fold) in TNF-α and ET-1 (1.6–4.0-fold), and a decrease (1.4–1.5-fold) in IL-4. However, the group on the alcohol diet exhibited a 38.3% higher mucosal expression of TNF-α, a 26.2% higher ET-1 level, and a 6.5% lower content of IL-4. While in both groups the ulcer healing was accompanied by an increase in buccal mucosal expression of IL-4, and a decline in ET-1 and TNF-α, the changes were significantly slower in the alcohol diet group and manifested by a 4 day delay in ulcer healing. The results suggest that chronic alcohol ingestion exerts detrimental effects on the buccal mucosal IL-4 expression, causing dysregulation of ET-1 production, induction of TNF-α, and triggering apoptotic events that delay the mucosal repair.