20.500.12556/RUL-165389 MyD88 protein destabilization mitigates NF-κB-dependent protection against macrophage apoptosis 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 prone to apoptosis, exacerbated by ibrutinib treatment. NF-κB activation by lipopolysaccharide mitigated this sensitive phenotype. These findings underscore the importance of MyD88$^{wt}$ signaling for NF-κB activation, protecting against macrophage premature apoptosis at resting state. Targeting MyD88 quantity rather than just its signaling could be a promising strategy for MyD88-driven lymphoma treatment. MyD88 NF-κB signaling apoptosis homeostasis oxidative stress imunologija makrofagi apoptaza homeostaza oksidativni stres MyD88 true false true Angleški jezik Slovenski jezik Članek v reviji 2024-12-05 04:02:01 2024-12-05 09:38:29 2025-11-25 11:07:13 0000-00-00 00:00:00 2024 0 0 14 str. art. 549 Vol. 22 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577.27 1478-811X 10.1186/s12964-024-01930-1 215726595 RAZ_Lainscek_Dusko_2024.pdf RAZ_Lainscek_Dusko_2024.pdf 1 C1CCF104C1B6A428A18CA9029C4669BC dde021d0331cf5937cc881bc3e84d3d194617ba764b6be4b5c549a2f98deb287 9ad538df-b2e4-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196527 https://biosignaling.biomedcentral.com/articles/10.1186/s12964-024-01930-1 1 dab382ee-b2b4-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196521 Biotehniška fakulteta Medicinska fakulteta 0 0 0