Correlation analysis of cytokine gene expression changes and antiulcer effects of Pro-Gly-Pro and N-Acetyl-Pro-Gly-Pro in experimental models of ulceration.

Direct correlation of the cytokine gene expression level in peripheral blood mononuclear cells (BMNCs) and gastric mucosa (GM) cells with the development of gastric ulcers of various etiologies was shown for the first time. Ethanol-induced ulceration causes an increased transcription of IFNa, IL-8, and IL-12 mRNA in BMNCs. GM damages caused by water immersion stress were accompanied by an increased transcription of TNFa. The sizes of acetate-induced damages were positively correlated with the expression of IL-10 and IL-8 genes in BMNCs and with the expression of IFNa, IL-2, IL-12, and TNF genes in GM cells. Intranasal administration of Pro-Gly-Pro (PGP) reduced ethanol-induced ulceration, activating the transcription of IFNγ, IL-2, and IL-4 mRNA in BMNCs and prevents the formation of stress- and acetateinduced ulcers by inhibiting the expression of IL-8 and IL-10 genes, respectively.