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

Lainšček, Duško (avtor), Horvat, Simon (avtor), Dolinar, Klemen (avtor), Ivanovski, Filip (avtor), Romih, Rok (avtor), Pirkmajer, Sergej (avtor), Jerala, Roman (avtor), Manček Keber, Mateja (avtor)

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 MyD88D162E 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 MyD88wt counterparts, MyD88D162E 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 MyD88wt 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.

• Jezik: Angleški jezik
• Ključne besede: MyD88, NF-κB signaling, apoptosis, homeostasis, oxidative stress
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: BF - Biotehniška fakulteta ; MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 14 str.
• Številčenje: Vol. 22, art. 549
• PID: 20.500.12556/RUL-165389
• UDK: 577.27
• ISSN pri članku: 1478-811X
• DOI: 10.1186/s12964-024-01930-1
• COBISS.SI-ID: 215726595
• Datum objave v RUL: 05.12.2024

Gradivo je del revije

• Naslov: Cell communication and signaling
• Skrajšan naslov: Cell commun. signal.
• Založnik: BioMed Central
• ISSN: 1478-811X
• COBISS.SI-ID: 513859097

Licence

• Licenca: CC BY-NC-ND 4.0, Creative Commons Priznanje avtorstva-Nekomercialno-Brez predelav 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc-nd/4.0/deed.sl
• Opis: Najbolj omejujoča licenca Creative Commons. Uporabniki lahko prenesejo in delijo delo v nekomercialne namene in ga ne smejo uporabiti za nobene druge namene.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: imunologija, makrofagi, apoptaza, homeostaza, oksidativni stres, MyD88