2. Academic Validation
  3. Palmitoylation of NLRP3 Modulates Inflammasome Activation and Inflammatory Bowel Disease Development

Palmitoylation of NLRP3 Modulates Inflammasome Activation and Inflammatory Bowel Disease Development

  • J Immunol. 2024 Jul 1:ji2300241. doi: 10.4049/jimmunol.2300241.
Dingwen Hu 1 2,  Yuting Li 3,  Xianyang Wang 3,  Haimei Zou 3,  Zonghui Li 3,  Weijie Chen 4,  Yu Meng 3,  Yingchong Wang 2,  Qin Li 2,  Feng Liao 3,  Kailang Wu 2,  Jianguo Wu 2 4,  Geng Li 3 4,  Wenbiao Wang 5
Affiliations

Affiliations

  • 1 Clinical Experimental Center, Jiangmen Central Hospital, Jiangmen, China.
  • 2 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • 3 Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
  • 4 Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China.
  • 5 Medical Research Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
PMID: 38949555 DOI: 10.4049/jimmunol.2300241
Abstract

Aberrant activity of NLRP3 has been shown associations with severe diseases. Palmitoylation is a kind of protein post-translational modification, which has been shown to regulate Cancer development and the innate immune system. Here, we showed that NLRP3 is palmitoylated at Cys419 and that palmitoyltransferase ZDHHC17 is the predominant Enzyme that mediates NLRP3 palmitoylation and promotes NLRP3 activation by interacting with NLRP3 and facilitating NIMA-related kinase 7 (NEK7)-NLRP3 interactions. Blockade of NLRP3 palmitoylation by a palmitoylation inhibitor, 2-bromopalmitate, effectively inhibited NLRP3 activation in vitro. Also, in a dextran sulfate sodium-induced colitis model in mice, 2-bromopalmitate application could attenuate weight loss, improve the survival rate, and rescue pathological changes in the colon of mice. Overall, our study reveals that palmitoylation of NLPR3 modulates inflammasome activation and inflammatory bowel disease development. We propose that drugs targeting NLRP3 palmitoylation could be promising candidates in the treatment of NLRP3-mediated inflammatory diseases.

Figures
Products