Pirfenidone activates cannabinoid receptor 2 in a mouse model of bleomycin‑induced pulmonary fibrosis

Liu,Jinhong; Shi,Guiling

doi:10.3892/etm.2019.8045

Pirfenidone activates cannabinoid receptor 2 in a mouse model of bleomycin‑induced pulmonary fibrosis

Authors:
- Jinhong Liu
- Guiling Shi
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Affiliations: Department of Pharmacy, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, P.R. China, Department of Pharmacy, Tianjin People's Hospital, Tianjin 300121, P.R. China
Published online on: September 25, 2019 https://doi.org/10.3892/etm.2019.8045
Pages: 4241-4248
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Inflammation serves an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Cannabinoid receptor 2 (CB2R) is a receptor predominantly expressed in the immune system. CB2R agonists can be used to treat a wide range of inflammation‑related diseases. Pirfenidone has been demonstrated to be effective for IPF treatment. The aim of present study was to investigate whether CB2R activation mediates the antifibrotic effect of pirfenidone. For that purpose, mice were intravenously injected with bleomycin (BLM; 5 mg/kg/day). pirfenidone (300 mg/kg/day) was then orally administered for 15 days. Lung pathological alterations in the mice were evaluated by Masson's trichrome staining. The mRNA and protein levels of CB2R in lung tissues were measured by reverse transcription‑quantitative PCR and western blotting. The levels of inflammatory factors were determined by ELISA. The effect of pirfenidone on WI38 cell viability was evaluated by MTT assay. The results demonstrated that CB2R protein and mRNA levels increased with increasing fibrosis in mice with BLM‑induced IPF. Pirfenidone administration significantly ameliorated IPF and reduced the serum levels of inflammatory factors induced by BLM. Pirfenidone also inhibited fibroblast cell proliferation and decreased the levels of inflammatory factors in vitro, which could be reversed by the CB2R antagonist SR144528, suggesting that CB2R was activated by pirfenidone. In conclusion, pirfenidone attenuated and activated CB2R in BLM‑treated mice. In addition, pirfenidone inhibited fibroblast cell proliferation in vitro. These effects could be reversed by the CB2R antagonist SR144528. Thus, activation of CB2R may be considered a mechanism of the antifibrotic effects of pirfenidone.

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