The NALP3 inflammasome is required for collagen synthesis via the NF‑κB pathway

Kuang,Ju; Xie,Min; Wei,Xiaolin

doi:10.3892/ijmm.2018.3404

The NALP3 inflammasome is required for collagen synthesis via the NF‑κB pathway

Authors:
- Ju Kuang
- Min Xie
- Xiaolin Wei
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Affiliations: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
Published online on: January 18, 2018 https://doi.org/10.3892/ijmm.2018.3404
Pages: 2279-2287

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Abstract

The NALP3 inflammasome interacts with various immune and cell metabolic pathways and may participate in pulmonary fibrosis. However, little is known on its regulatory mechanism with respect to collagen synthesis. The objective of the present study was to investigate whether NALP3 inflammasome activation is involved in H2O2‑mediated collagen synthesis, in addition to examining the possible cell signaling mechanisms underlying this effect. It was demonstrated that the NF‑κB signaling pathway was activated under conditions of H2O2‑mediated oxidative stress in NIH‑3T3 mouse embryonic fibroblasts. H2O2‑exposed fibroblasts exhibited activated NALP3 inflammasomes via increased NALP3, apoptosis‑associated Speck‑like protein and caspase‑1 expression and the secretion of interleukin‑1β. H2O2 also elevated α‑SMA and type I collagen expression. In vitro silencing of NALP3 attenuated the degradation of IκBα and decreased the synthesis of type I collagen. Furthermore, the NALP3 inflammasome was found to be activated in bleomycin‑induced pulmonary fibrosis in mice, and this activation was relieved by a nuclear factor (NF)‑κB inhibitor. Taken together, these findings indicate that the NALP3 inflammasome is involved in H2O2‑induced type I collagen synthesis, which is mediated by the NF‑κB signaling pathway. Additionally, the NALP3 inflammasome contributes to the development of bleomycin‑induced pulmonary fibrosis.

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