Valsartan attenuates bleomycin-induced pulmonary fibrosis by inhibition of NF-κB expression and regulation of Th1/Th2 cytokines.

Valsartan attenuates bleomycin-induced pulmonary fibrosis by inhibition of NF-κB expression and regulation of Th1/Th2 cytokines.

Immunopharmacol Immunotoxicol. 2018 Feb 15;:1-7

Authors: Mojiri-Forushani H, Hemmati AA, Khodadadi A, Rashno M

Abstract
OBJECTIVE: Pulmonary fibrosis (PF) is a chronic respiratory system disease. The role of inflammation and angiotensin in the development and progression of PF has previously been demonstrated. Alternation in antifibrotic/profibrotic mediators and NF-κB activation have important roles in PF development. NF-κB, a nuclear factor, induces the transcription of inflammatory and pro-inflammatory cytokines. The aim of this study was to evaluate the effect of valsartan as an angiotensin receptor blocker on IL-4, INF-γ, and NF-κB expression in the treatment of PF.
MATERIALS AND METHODS: Rats were divided into five groups: groups I (bleomycin) and II (control) received a single injection of bleomycin (7.5 IU/kg) or vehicle, respectively. Groups III-V received valsartan (20, 40, and 80 mg/kg, respectively) orally a week before and for 3 weeks after the bleomycin injection. Serum levels of IL-4 and INF- γ were then measured. Relative NF-κB expression was investigated by real-time PCR.
RESULTS: Histopathological examination showed the anti-inflammation effect of valsartan. Bleomycin significantly increased IL-4 serum level and decreased that of INF-γ in the serum. Valsartan could restore their levels to normal. Valsartan raised the decreased ratio of INF-γ/IL-4. Exposure to bleomycin elevated NF-κB expression; and valsartan decreased the increased gene expression.
DISCUSSION: Valsartan as an angiotensin receptor antagonist presumably by blocking angiotensin receptor causes to ameliorated PF, which was at least partly due to antifibrotic/profibrotic cytokine regulation and reduced NF-κB expression.
CONCLUSIONS: Valsartan showed a significant protective effect against bleomycin-induced PF.

PMID: 29447007 [PubMed - as supplied by publisher]

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