MyD88 protein destabilization mitigates NF-κB-dependent protection against macrophage apoptosis.

ABSTRACT: Various signaling pathways are essential for both the innate immune response and the maintenance of cell homeostasis, requiring coordinated interactions among them. In this study, a mutation in the caspase-1 recognition site within MyD88 abolished inflammasome-dependent negative regulation, causing phenotypic changes in mice with some similarities to human NEMO-deficiencies. The MyD88^D162E mutation reduced MyD88 protein levels and colon inflammation in DSS-induced colitis mice but did not affect cytokine expression in bone marrow-derived macrophages (BMDMs). However, compared to MyD88^wt counterparts, MyD88^D162E BMDMs had increased oxidative stress and dysfunctional mitochondria, along with reduced prosurvival Bcl-xL and BTK expression, rendering cells more

SUBMITTER: Lainscek D 

PROVIDER: S-EPMC11568545 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature