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Int. J. Mol. Sci. 2015, 16(9), 20195-20211; doi:10.3390/ijms160920195

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

1,2,†
,
2,†
,
3,†
and
2,*
1
Department of Respiratory Medicine, ZhuJiang Hospital, Southern Medical University, Guangzhou 510280, China
2
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
3
Department of Respiratory Medicine, First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 21 June 2015 / Revised: 23 July 2015 / Accepted: 16 August 2015 / Published: 26 August 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
View Full-Text   |   Download PDF [3028 KB, uploaded 26 August 2015]   |  

Abstract

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. View Full-Text
Keywords: asthma; glucagon like peptide-1 (GLP-1); liraglutide; E-selectin; MUC5AC; protein kinase A (PKA); nuclear factor-κB (NF-κB) asthma; glucagon like peptide-1 (GLP-1); liraglutide; E-selectin; MUC5AC; protein kinase A (PKA); nuclear factor-κB (NF-κB)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Zhu, T.; Wu, X.-L.; Zhang, W.; Xiao, M. 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. Int. J. Mol. Sci. 2015, 16, 20195-20211.

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