Pirfenidone activates cannabinoid receptor 2 in a mouse model of bleomycin-induced pulmonary fibrosis.
Exp Ther Med
; 18(6): 4241-4248, 2019 Dec.
Article
em En
| MEDLINE
| ID: mdl-31777533
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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MEDLINE
Tipo de estudo:
Prognostic_studies
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En
Ano de publicação:
2019
Tipo de documento:
Article