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Raltegravir Attenuates Experimental Pulmonary Fibrosis In Vitro and In Vivo

Authors :
Haidi Huang
Zhang Guanghua
Zhang Xue
Hongbo Wang
Wanglin Jiang
Defang Li
Source :
Frontiers in Pharmacology, Frontiers in Pharmacology, Vol 10 (2019)
Publication Year :
2019
Publisher :
Frontiers Media S.A., 2019.

Abstract

Raltegravir, an inhibitor of human immunodeficiency virus-1 (HIV-1) integrase, has been used to treat HIV/acquired immunodeficiency syndrome; however, its therapeutic effects on pulmonary fibrosis have not been investigated. In this study, the in vitro effects of raltegravir (RAV) on transforming growth factor beta 1 (TGF-β1)-induced pulmonary fibrosis on L929 mouse fibroblasts were investigated. In addition, the effects of RAV on an in vivo pulmonary fibrosis model induced by intratracheal instillation of bleomycin were investigated. The proliferation of L929 cells was inhibited after RAV treatment. Meanwhile, the in vitro and in vivo protein expression of nucleotide-binding oligomerization domain-like receptor 3 (NLRP3), high-mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), prolyl hydroxylase domain protein 2, phosphorylated nuclear factor-κB (p-NF-κB), hypoxia-inducible factor-1α (HIF-1α), collagens I and III was reduced relative to TGF-β1 or the bleomycin group. Raltegravir ameliorated pulmonary fibrosis by reducing the pathology score, collagen deposition, and expression of α-smooth muscle actin, NLRP3, HMGB1, TLR4, inhibitor of kappa B, p-NF-κB, HIF-1α, collagen I, and collagen III. The results of this study demonstrate that RAV attenuated experimental attenuates pulmonary fibrosis by inhibiting NLRP3 activation.

Details

Language :
English
ISSN :
16639812
Volume :
10
Database :
OpenAIRE
Journal :
Frontiers in Pharmacology
Accession number :
edsair.doi.dedup.....33b76f4fef3bf2864b6956d8ad40f01e