title: Exendin-4 attenuates lipopolysaccharides induced inflammatory response but does not protects H9c2 cells from apoptosis.
abstract: 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.
authors: Department of Cardiology, Chang-Gung Memorial Hospital and Chang Gung University College of Medicine, Taipei, Taiwan.
authors: Tien-Hsing
authors: TH
authors: Chen
authors: Hung-Ta
authors: HT
authors: Wo
authors: Chien-Chia
authors: CC
authors: Wu
authors: Jian-Liang
authors: JL
authors: Wang
authors: Chun-Chieh
authors: CC
authors: Wang
authors: I-Chang
authors: IC
authors: Hsieh
authors: Cheng-Yi
authors: CY
authors: Kuo
authors: Chien Ting
authors: CT
authors: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D000077270:Exenatide; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D032386:Myoblasts, Cardiac / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010455:Peptides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014688:Venoms / Q000494:pharmacology*
chemical_list: D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D014688:Venoms; D000077270:Exenatide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D020780:Matrix Metalloproteinase 9