glucagon-like-peptide-1 and Pulmonary-Fibrosis

To investigate the potential value and mechanisms of glucagon like peptide-1 (GLP-1) on bleomycin (BLM)-induced pulmonary fibrosis in mice.. Mice were treated with a single sublethal dose of BLM (3 mg/kg ) via intratracheal infusion to produce pulmonary fibrosis, and then liraglutide (2 mg/kg) was given to the mice for 28 days by intraperitoneal injection. 28 days after BLM infusion, the number of total cells, macrophages and neutrophils, lymphocytes, and the content of transforming growth factor-beta 1 (TGF-β1) in bronchoalveolar lavage fluid (BALF) were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. Real time(RT)-qPCR and Western blot were used to evaluate the expression of α-smooth muscle actin (α-SMA) and vascular cell adhesion molecule-1 (VCAM-1). The phosphorylation of nuclear factor-kappa B (NF-κB) p65 was also assessed by Western blot. DNA binding of NF-κB p65 was measured through TransAM. BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-κB.

Topics: Actins; Animals; Bleomycin; Bronchoalveolar Lavage Fluid; Glucagon-Like Peptide 1; Inflammation; Lung; Mice; Pulmonary Fibrosis; Transcription Factor RelA; Transforming Growth Factor beta1; Vascular Cell Adhesion Molecule-1

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with high mortality and poor prognosis. Previous studies confirmed that NF-κB plays a critical role in the pathogenesis of pulmonary fibrosis and glucagon like peptide-1 (GLP-1) has a property of anti-inflammation by inactivation of NF-κB. Furthermore, the GLP-1 receptor was detected in the lung tissues. Our aim was to investigate the potential value and mechanisms of GLP-1 on BLM-induced pulmonary fibrosis in mice. Mice with BLM-induced pulmonary fibrosis were treated with or without GLP-1 administration. 28 days after BLM infusion, the number of total cells, macrophages, neutrophils, lymphocytes, and the content of TGF-β1 in BALF were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. RT-qPCR and western blot were used to evaluate the expression of α-SMA and VCAM-1. The phosphorylation of NF-κB p65 was also assessed by western blot. DNA binding of NF-κB p65 was measured through Trans(AM) p65 transcription factor ELISA kit. GLP-1 reduced inflammatory cell infiltration and the content of TGF-β1 in BLAF in mice with BLM injection. The Ashcroft score and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM-induced overexpression of α-SMA and VCAM-1 were blocked by GLP-1 treatment in mice. GLP-1 also reduced the ratio of phosphor-NF-κB p65/total-NF-κB p65 and NF-κB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice. Our data found that BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-κB.

Topics: Actins; Animals; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Bleomycin; Bronchoalveolar Lavage Fluid; Cell Count; Collagen; DNA; Glucagon-Like Peptide 1; Hydroxyproline; Lung; Male; Mice, Inbred C57BL; NF-kappa B; Pulmonary Fibrosis; Transcription Factor RelA; Transforming Growth Factor beta1; Vascular Cell Adhesion Molecule-1