MyD88 mediates the decision to die by apoptosis or necroptosis after UV irradiation:

Innate Immunity

ErinHarberts¹ 

关键词: MyD88;    ultraviolet irradiation;    apoptosis;    necroptosis;    TLR4;   

DOI  :  10.1177/1753425913501706

学科分类：生物科学（综合）

来源: Sage Journals

【 摘 要 】

UV irradiation-induced cellular damage is classically associated with apoptosis and is known to result in systemic immunosuppression. How the decision to undergo apoptosis is made following UV is not fully understood. We hypothesize that a central mediator of TLR signaling, MyD88, determines cell fate after UV exposure. Survival after UV of immortalized bone marrow-derived macrophages (BMDM) and ex vivo peritoneal macrophages (PM) from MyD88 germline-deficient mice (MyD88-/-) was significantly higher than wild type (WT) PM. UV-induced apoptosis (DNA laddering) in PM and epidermis of MyD88-/- animals versus WT was decreased. In MyD88-/- PM, decreased cleavage of caspase 3, as well as pro-necroptotic protein, RIP1, and a significant increase in transcription and release of pro-inflammatory TNF-α, suggest that necroptosis, rather than apoptosis, has been initiated. In vivo studies confirm this hypothesis after UV, showing low apoptosis by TUNEL and inflammation in MyD88-/- skin sections. Considering that MyD...

【 授权许可】

CC BY