MyD88 plays a role in deciding between apoptotic and necroptotic cell death after UV irradiation (P1238)
| Autor: | Erin Harberts, Rita Fishelevich, Juan Liu, Sergei Atamas, Anthony Gaspari |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:138.17-138.17 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Ultraviolet irradiation (UV) induced cellular damage is classically associated with apoptosis and 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. Survival after UV of immortalized bone marrow-derived macrophages (BMM) from MyD88 germline-deficient mice (MyD88-/-) was significantly higher and apoptotic morphology reduced, vs. wild-type (WT) BMM. UV-induced DNA laddering in peritoneal macrophages (PM) and epidermis of MyD88-/- animals, vs. WT, was decreased. In MyD88-/- PM, decreased cleavage of pro-necroptotic protein RIP1, elevated mRNA levels of RIP1 and RIP3, and significantly increased TNF-α release suggests that necroptosis rather than apoptosis has been initiated. In vivo studies after UV showed significantly less TUNEL-positive cells and more profound inflammation in MyD88-/- skin sections. MyD88-/- mice are also found to be resistant to UV-induced immunosuppression. Considering that MyD88 participates in many TLR pathways, TLR2-/-, TLR4-/-, and WT BMM were compared for evidence of UV-induced apoptosis. Only TLR4-/- BMM had a similar phenotype to MyD88-/-, suggesting that the TLR4-MyD88 axis importantly contributes to cell fate decision. Our study describes a new cellular consequence of MyD88 signaling after UV, and may provide rationale for therapies to mitigate UV-induced immunosuppression. |
| Databáze: | OpenAIRE |
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