9a, a novel synthetic histone deacetylase inhibitor, protects against @entity130 by suppressing MAPK signaling in XXXX .

@entity19 @entity1995 @entity12231 @entity777 @entity12147 @entity842 @entity17311 @entity1990 @entity204 @entity637 @entity130
BACKGROUND AND PURPOSE: Sepsis is a life-threatening clinical condition characterized by uncontrolled inflammatory responses and is a major cause of @entity204 in intensive care units. Histone deacetylase (HDAC) inhibitors have recently exhibited anti-inflammatory properties. MAPK phosphatase (MKP) suppresses MAPK signaling, which plays an important role in inflammatory responses. The purpose of this study was to investigate the protective mechanisms of 9a, a new synthetic HDAC inhibitor, against @entity130 . EXPERIMENTAL APPROACH: The anti-inflammatory properties of 9a were assayed in LPS-stimulated RAW264.7 cells. Polymicrobial sepsis was induced in C57BL/6 @entity19 by cecal ligation and puncture ( @entity12147 ). The @entity19 were i.p. administered 9a (10 mg   kg-1) 2 h before and immediately after @entity12147 . KEY RESULTS: 9a inhibited the increased production of @entity637 , @entity777 , and @entity842 in LPS-stimulated RAW264.7 cells. 9a improved survival rate, attenuated organ injuries, and decreased serum @entity637 and @entity777 levels. @entity12147 increased expression of @entity1990 , phosphorylated (p)- @entity1995 , p-JNK, and p-ERK proteins, which was attenuated by 9a. 9a decreased @entity17311 association with @entity12231 and enhanced @entity17311 acetylation and enhanced @entity17311 association with p- @entity1995 and p-ERK. Moreover, the inhibitory effects of 9a on serum cytokine levels and phosphorylation of MAPK were abolished by @entity17311 siRNA. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that 9a protects against @entity130 by suppressing MAPK-mediated inflammatory signaling. This article is protected by copyright. All rights reserved.
