DNMT and HDAC inhibitors together abrogate endotoxemia mediated macrophage death by STAT3-JMJD3 signaling.

ABSTRACT: Acute lung injury (ALI) is a common complication of sepsis that often leads to fatal lung disease without effective therapies. It is known that bone marrow derived macrophages are important in resolving the inflammation and maintaining tissue homeostasis. Here, we hypothesize that treatment in combination of DNA methyl transferase inhibitor (DNMTi) 5-Aza 2-deoxycytidine (Aza) and histone deacetylase inhibitor (HDACi) Trichostatin A (TSA) mitigates the inflammation induced pyroptosis and apoptosis during endotoxemia induced ALI. To test this hypothesis, the mice challenged with a sublethal dose of LPS followed by one-hour post-treatment with a single dose of Aza and TSA intraperitoneally showed a substantial attenuation of apoptosis and inflammation. Importantly, we observed significant cha

SUBMITTER: Samanta S 

PROVIDER: S-EPMC6309960 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature