Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

Δευτέρα 18 Δεκεμβρίου 2017

Embryonic Lethality and Host Immunity of RelA-Deficient Mice Are Mediated by Both Apoptosis and Necroptosis [INNATE IMMUNITY AND INFLAMMATION]

In mammalian cells, signaling pathways triggered by TNF can be switched from NF-B activation to apoptosis and/or necroptosis. The in vivo mechanisms underlying the mutual regulation of these three signaling pathways are poorly understood. In this article, we report that the embryonic lethality of RelA-deficient mice is partially prevented by the deletion of Rip3 or Mlkl, but it is fully rescued by the combined ablation of Fadd and Rip3 or Mlkl or by blocking RIP1 kinase activity (RIP1K45A). RelA–/–Fadd–/–Rip3–/– triple-knockout (TKO) and RelA–/–Rip1K45A/K45A mice displayed bacterial pneumonia leading to death ~2 wk after birth. Moreover, RelA–/–Rip1K45A/K45A mice, but not TKO mice, developed severe inflammation associated with inflammatory skin lesion. Antibiotic treatment improved bacterial pneumonia, extended the lifespan of TKO and RelA–/–Rip1K45A/K45A mice, and alleviated skin inflammation in RelA–/–Rip1K45A/K45A mice. These results show the mechanisms underlying the in vivo mutual regulation between NF-B activation and the cell death pathway and provide new insights into this interplay in embryonic development and host immune homeostasis.



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