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

作者：Renle Chang, Jiejie Sun, Jinyuan Leng, Zihan Wang, Shuyi Mu, Yinan Li, Jie Wang, Linsheng Song · 发表于：Communications Biology · 年份：2025 · DOI：10.1038/s42003-025-08290-7 · 被引用次数：7 · 研究领域：Inflammasome and immune disorders、NF-κB Signaling Pathways、Cell death mechanisms and regulation

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. In the present study, CgCas1-2D, a new type of anti-inflammatory Caspase-1 identified from oysters, interacts with GSDME upon recognizing various bacteria to inhibit the histone modification and NF-κB signaling to suppress the inflammation.