Glucagon like peptide-1 attenuates bleomycin-induced pulmonary fibrosis, involving the inactivation of NF-κB in mice.

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.

Gou S ，Zhu T ，Wang W ，Xiao M ，Wang XC ，Chen ZH ... -  《-》

[The Study of the Effect and Mechanism of Glucagon Like Peptide-1 in Bleomycin-induced Pulmonary Fibrosis in Mice].

Liu M ，Gou S ，Chen HT ，Chen ZH ... -  《-》

Protective role of andrographolide in bleomycin-induced pulmonary fibrosis in mice.

Zhu T ，Zhang W ，Xiao M ，Chen H ，Jin H ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

[Effects of antisense oligonucleotide to nuclear factor-kappaB on the development of bleomycin-induced pulmonary fibrosis and IL-4 expression therein: experiment with mice].

Zhang XY ，Zhou Y ，Liu WQ ，Zhao L ，Li SQ ... -  《-》

Hydrogen sulfide protects against bleomycin-induced pulmonary fibrosis in rats by inhibiting NF-κB expression and regulating Th1/Th2 balance.

Hydrogen sulfide (H2S) displays vasodilative, anti-oxidative, anti-inflammatory and cytoprotective activities. The objective of this study was to evaluate the inhibitory effect of H2S on bleomycin (BLM)-induced pulmonary fibrosis in rats and its possible mechanisms. Fifty-four pathogen-free Male Wistar rats were randomly divided into three groups: control, BLM and H2S treated groups with 18 rats in each group. Each group was then divided into three subgroups based on time of study (7, 14 and 28 day). Pulmonary fibrosis model was established by a single intratracheal instillation of BLM A5 (5 mg/kg). While control rats received saline, rats of the treated group simultaneously were administered intraperitoneal injections of NaHS (the H2S donor, 28 μmol/kg) once daily. BLM induced pulmonary inflammation and fibrosis, increased lung hydroxyproline levels, lung index, total cell counts, neutrophils and eosinophils counts and expression of NF-κB p65 in lung tissue, decreased lymphocytes and macrophages counts. In addition, Th1 response is suppressed as shown by diminished IFN-γ in bronchoalveolar lavage fluid (BALF) after BLM exposure, and enhancement of Th2 response is marked by increased IL-4 in BALF. H2S administration significantly attenuated these effects. The findings reveal the therapeutic potential of H2S for BLM-induced pulmonary fibrosis in male rats, which were at least partly due to inhibition NF-κB p65 expression and regulation of Th1/Th2 balance.

Cao H ，Zhou X ，Zhang J ，Huang X ，Zhai Y ，Zhang X ，Chu L ... -  《-》