2. Academic Validation
  3. A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling

A new type of Caspase-1 upon recognizing bacteria inhibits GSDME-dependent histone modification and NF-κB signaling

  • Commun Biol. 2025 May 29;8(1):827. doi: 10.1038/s42003-025-08290-7.
Renle Chang # 1 2 3,  Jiejie Sun # 4 5 6,  Jinyuan Leng 1 2 3,  Zihan Wang 1 2 3,  Shuyi Mu 1 2 3,  Yinan Li 1 2 3,  Jie Wang 1 2 3,  Linsheng Song 7 8 9
Affiliations

Affiliations

  • 1 Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China.
  • 2 Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China.
  • 3 Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China.
  • 4 Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China. sunjiejie@dlou.edu.cn.
  • 5 Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China. sunjiejie@dlou.edu.cn.
  • 6 Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China. sunjiejie@dlou.edu.cn.
  • 7 Liaoning Key Laboratory of Marine Animal Immunology, Dalian Ocean University, Dalian, China. lshsong@dlou.edu.cn.
  • 8 Liaoning Key Laboratory of Marine Animal Immunology & Disease Control, Dalian Ocean University, Dalian, China. lshsong@dlou.edu.cn.
  • 9 Dalian Key Laboratory of Aquatic Animal Diseases Prevention and Control, Dalian Ocean University, Dalian, China. lshsong@dlou.edu.cn.
  • # Contributed equally.
PMID: 40442231 DOI: 10.1038/s42003-025-08290-7
Abstract

In the present study, a new type of Caspase-1 homolog is identified from Crassostrea gigas (defined as CgCas1-2D). It is composed of 2×DSRM-CASc domain and has closer evolutionary relationship with mammalian Caspase-1s. The mRNA expressions of CgCas1-2D increase significantly after Vibrio splendidus or LPS stimulation. Recombinant CgCas1-2D and its 2×DSRM and CASc domains all bind various PAMPs and bacteria. rCgCas1-2D shows the highest binding activity to human Caspase-1 substrate. Upon recognizing bacteria, CgCas1-2D co-localizes and interacts with CgGSDME, while it has no cleavage activity to CgGSDME. CgCas1-2D inhibits the histone methylation and acetylation levels and CgNF-κB/Rel nuclear translocation mediated by CgGSDME. In addition, CgCas1-2D suppresses the mRNA expression levels of cytokines mediated by GSDME-NF-κB/Rel axis. The results demonstrate that a new type of anti-inflammatory Caspase-1 identified from oyster upon recognizing various bacteria interacts with GSDME to inhibit the histone modification and NF-κB signaling to suppress the inflammation.

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