Exendin-4 attenuates lipopolysaccharides induced inflammatory response but does not protects H9c2 cells from apoptosis.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its analogues are reported to exert wide-ranging cardiovascular actions in preclinical and clinical studies. We thus investigated whether the GLP-1 receptor agonist, exendin-4, has inhibitory effects on LPS-stimulated inflammatory response in cardiomyoblasts. METHODS: H9c2 cardiomyoblasts were exposed to LPS and treated with exendin-4. Expressions of proinflammatory mediators were assessed using quantitative real-time PCR. Nuclear localization of NF-κB was examined using immunoblotting. mRNA expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production were evaluated by q PCR and NO assay. Furthermore, anti-apoptotic effect of exendin-4 in LPS-stimulated H9c2 cells was determined using qPCR and immunoblot. RESULTS: Exposure to LPS increased mRNA expressions of TNF-α, COX-2 and MMP-9 in H9c2 cells. It also caused increases in iNOS mRNA expression and NF-κB nuclear translocation. Exendin-4 dose-dependently downregulated mRNA levels of TNF-α, COX-2 and MMP-9 in LPS-stimulated H9c2 cells. It also reduced NF-κB nuclear translocation. Treatment with exendin-4 showed no effect on LPS-induced apoptosis in H9c2 cells. CONCLUSIONS: Exendin-4 exerts an effect on cardiomyoblast exposed to LPS by inhibiting mRNA expression of inflammatory mediators and suppressing NF-κB activation. These effects are consistent with some of the observed anti-inflammatory properties of exendin-4, as well as its beneficial actions on the cardiovascular system.