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Activation of the NLRP3 inflammasome by HMGB1 through inhibition of the Nrf2/HO-1 pathway promotes bleomycin-induced pulmonary fibrosis after acute lung injury in rats
Huang, Ying; Wang, Aili; Jin, Sheng; Liu, Fang; Xu, Fang.
Afiliação
  • Huang, Ying; Wuhan No. 1 Hospital. Department of Respiratory and Critical Care Medicine. Wuhan. China
  • Wang, Aili; Wuhan No. 1 Hospital. Department of Respiratory and Critical Care Medicine. Wuhan. China
  • Jin, Sheng; Hubei No. 3 People’s Hospital of Jianghan University. Nephrology Department of Integrated Traditional Chinese and Western Medicine. Wuhan. China
  • Liu, Fang; Hubei No. 3 People’s Hospital of Jianghan University. Department of Respiratory Medicine. Wuhan. China
  • Xu, Fang; Wuhan No. 1 Hospital. Department of Respiratory and Critical Care Medicine. Wuhan. China
Allergol. immunopatol ; 51(3): 56-67, 01 mayo 2023. tab
Article em En | IBECS | ID: ibc-219814
Biblioteca responsável: ES1.1
Localização: ES15.1 - BNCS
ABSTRACT
Objective: Acute lung injury (ALI) is a common complication of critical diseases with high morbidity and mortality. This study explored the regulatory role and mechanism of high mobility histone box 1 protein (HMGB1) on pulmonary fibrosis (PF) after ALI in rats through nucleotide oligomerization domain-like receptor protein-3 (NLRP3) inflammasome. Methods: PF rat models after ALI were established by induction of bleomycin. Degree of fibrosis was assessed by Masson staining and Ashcroft scoring. Hydroxyproline (Hyp) contents in lung tissues and rat lung tissue morphology were detected by enzyme-linked-immunosorbent serologic assay (ELISA) and hematoxylin and eosin staining. The levels of NLRP3, major proteins of NLRP3 inflammasome (NLRP3/ASC/caspase-1), and downstream inflammatory cytokines interleukin (IL)-1 and IL-18 were determined using immunohistochemistry, Western blotting analysis, and ELISA. The nuclear/cytoplasmic nuclear factor erythroid 2-related factor 2 (Nrf2) levels and HO-1 levels were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting analysis. Rats was injected with lentivirus carrying short hairpin (sh)-HMGB1 and zinc protoporphyria (ZNPP) (HO-1 inhibitor) to assess the effects of HMGB1 and HO-1 on PF and NLRP3 inflammasome activation. Results: Bleomycin induced PF after ALI in rats, manifested as patchy fibrosis, atelectasis, and excessive expansion, and increased Aschcroft score and Hyp content. Bleomycin treatment enhanced levels of NLRP3, ASC, caspase-1, IL-1, and IL-18 in rat lung tissues, which promoted activation of NLRP3 inflammasome. HMGB1 was up-regulated in bleomycin-induced rats. HMGB1 knockdown partially reversed NLRP3 inflammasome activation and PF progression (AU)
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Texto completo: 1 Coleções: 06-national / ES Base de dados: IBECS Assunto principal: Fibrose Pulmonar / Proteína HMGB1 / Fator 2 Relacionado a NF-E2 / Lesão Pulmonar Aguda / Inflamassomos / Proteína 3 que Contém Domínio de Pirina da Família NLR Limite: Animals / Humans / Male Idioma: En Revista: Allergol. immunopatol Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 06-national / ES Base de dados: IBECS Assunto principal: Fibrose Pulmonar / Proteína HMGB1 / Fator 2 Relacionado a NF-E2 / Lesão Pulmonar Aguda / Inflamassomos / Proteína 3 que Contém Domínio de Pirina da Família NLR Limite: Animals / Humans / Male Idioma: En Revista: Allergol. immunopatol Ano de publicação: 2023 Tipo de documento: Article