Glucagon Like Peptide-1 (GLP-1) Modulates OVA-Induced Airway Inflammation and Mucus Secretion Involving a Protein Kinase A (PKA)-Dependent Nuclear Factor-κB (NF-κB) Signaling Pathway in Mice.
Asthma is a common chronic pulmonary inflammatory disease, featured with mucus hyper-secretion in the airway. Recent studies found that glucagon like peptide-1 (GLP-1) analogs, including liraglutide and exenatide, possessed a potent anti-inflammatory property through a protein kinase A (PKA)-dependent signaling pathway. Therefore, the aim of current study was to investigate the value of GLP-1 analog therapy liraglutide in airway inflammation and mucus secretion in a murine model of ovalbumin (OVA)-induced asthma, and its underlying molecular mechanism. In our study, BALB/c mice were sensitized and challenged by OVA to induce chronic asthma. Pathological alterations, the number of cells and the content of inflammatory mediators in bronchoalveolar lavage fluid (BALF), and mucus secretion were observed and measured. In addition, the mRNA and protein expression of E-selectin and MUC5AC were analyzed by qPCR and Western blotting. Then, the phosphorylation of PKA and nuclear factor-κB (NF-κB) p65 were also measured by Western blotting. Further, NF-κB p65 DNA binding activity was detected by ELISA. OVA-induced airway inflammation, airway mucus hyper-secretion, the up-regulation of E-selectin and MUC5AC were remarkably inhibited by GLP-1 in mice (all p < 0.01). Then, we also found that OVA-reduced phosphorylation of PKA, and OVA-enhanced NF-κB p65 activation and NF-κB p65 DNA binding activity were markedly improved by GLP-1 (all p < 0.01). Furthermore, our data also figured out that these effects of GLP-1 were largely abrogated by the PKA inhibitor H-89 (all p < 0.01). Taken together, our results suggest that OVA-induced asthma were potently ameliorated by GLP-1 possibly through a PKA-dependent inactivation of NF-κB in mice, indicating that GLP-1 analogs may be considered an effective and safe drug for the potential treatment of asthma in the future.
Department of Respiratory Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China. wuxiaoling2010@126.com.|Department of Respiratory Medicine, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu 610041, China. wuxiaoling2010@126.com.
Tao
T
Zhu
Department of Respiratory Medicine, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu 610041, China. wuxiaoling2010@126.com.
Xiao-Ling
XL
Wu
Department of Respiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China. zhangweicdmc@126.com.
Wei
W
Zhang
Department of Respiratory Medicine, and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital of Sichuan University, Chengdu 610041, China. xiaomin_wcms@163.com.
Min
M
Xiao
D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019040:E-Selectin / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009093:Mucus / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010047:Ovalbumin / Q000009:adverse effects / Q000276:immunology; D015398:Signal Transduction
D016207:Cytokines; D019040:E-Selectin; D018836:Inflammation Mediators; D016328:NF-kappa B; D052216:Glucagon-Like Peptide 1; D010047:Ovalbumin; D017868:Cyclic AMP-Dependent Protein Kinases
E-selectin; MUC5AC; asthma; glucagon like peptide-1 (GLP-1); liraglutide; nuclear factor-κB (NF-κB); protein kinase A (PKA)