RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury

Pei Yao Liu, Chih Yuan Chen, Yu Lung Lin, Chien Ming Lin, Wen Chiuan Tsai, Yu Ling Tsai, Gu Jiun Lin, Yu Guang Chen, Shih Yun Wang, Rui Nong Sun, Yu Chuan Huang, Hung Chang, Ying Chuan Chen

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Acute lung injury (ALI) is characterised by severe pulmonary inflammation, alveolar-capillary barrier disruption, and pulmonary oedema. Therefore, establishing effective therapeutic targets for ALI prevention is crucial. The present study reports a novel function of RNF128 in regulating LPS-induced ALI. Severe lung damage and increased immune cell infiltration were detected in RNF128-deficient mice. In vitro experiments revealed that RNF128 inhibits neutrophil activation by binding to myeloperoxidase (MPO) and reducing its levels and activity. Moreover, RNF128 regulates alveolar macrophage activation and neutrophil infiltration by interacting with TLR4, targeting it for degradation, and inhibiting NF-κB activation, hence decreasing pro-inflammatory cytokines. Our results demonstrate for the first time that RNF128 is a negative regulator of MPO and TLR4 in neutrophils and alveolar macrophages, respectively. However, AAV9-mediated RNF128 overexpression alleviated lung tissue damage and reduced inflammatory cell infiltration. Thus, RNF128 is a promising therapeutic candidate for pharmacological interventions in ALI.

Original languageEnglish
Article number369
JournalCell Death and Disease
Volume14
Issue number6
DOIs
Publication statusPublished - Jun 2023

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury'. Together they form a unique fingerprint.

Cite this