APIP regulates the priming of canonical NLRP3 and non-canonical Caspase-11/4 inflammasomes by binding to TRAF6.

ABSTRACT: Apaf-1-interacting protein (APIP) has been implicated in inflammation-related processes, including myocardial infarction and cancer progression. However, its role in systemic inflammation remains elusive. Here, we investigate the APIP-mediated regulation of inflammasome activity in mice and human macrophages. Loss of APIP in the myeloid lineage (Apip cKO mice) compromises the activation of canonical NLRP3 and non-canonical caspase-11 inflammasomes, reducing pyroptosis in bone marrow-derived macrophages (BMDM). Conversely, these inflammatory responses are enhanced in BMDMs from APIP-transgenic mice. Consistently, APIP knockdown in human macrophages inhibits the activation of NLRP3 and caspase-4 inflammasomes. Mechanistically, APIP binds to TRAF6, activating downstream NF-κB and JNK signalin

SUBMITTER: Jung K 

PROVIDER: S-EPMC12675500 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature