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ATF3 protects LPS‐induced acute pancreatic inflammation via modulating NFκB‐mediated iNOS production in mice
Author(s) -
Chen YuMin,
Tseng YaPing,
Liu ChinHung,
Lin Heng,
Cheng ChingFeng,
Lai PeiFang
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.657.2
Subject(s) - inflammation , proinflammatory cytokine , activating transcription factor , creb , lipopolysaccharide , endocrinology , nfkb1 , immunology , medicine , biology , transcription factor , biochemistry , gene
A state of excessive endotoxin (lipopolysaccharide, LPS) in the circulation is called endotoxemia. An overproduction of proinflammatory mediators in acute pancreatic inflammation, which may lead to insulin resistance, pancreas dysfunction and even death. Activating transcription factor (ATF)‐3, a subunit belongs to ATF/cAMP responsive element‐binding protein (CREB) family of transcription factor protects against stress‐induced acute kidney injury. The previous results suggest that ATF3 contributes to the negative regulation of inflammatory cytokine gene expression by recruiting histone deacetylase (HDAC)‐1 to ATF/NFκB‐binding sites. Biological activities and pathological effects of ATF3 in sepsis is unclear. The aim of this study is to assess the possible protective effects of ATF3 in endotoxemia induced by LPS in vivo studies. ATF3‐knockout (KO) and wild‐type mice (WT) were injected with LPS (10 mg/kg, ip) to induce endotoxemia. Survival rate in mouse model of endotoxemia, circulating white blood cells (WBC) level, serum NO expression, glucose level, histology, and the mRNA expression of inflammatory factors were investigated. The decreased circulating WBC levels, increased serum NO and glucose levels were significantly obtained in KO mice after LPS induction. Furthermore, inflammatory factor expressions, macrophage infiltration and β cell damage in KO mice after LPS induction were significantly reversed by injected adeno‐associated virus (AAV) to restore ATF3 gene expression. These results demonstrated that ATF3 plays a protective role to prevent LPS‐induced pancreas inflammation in experimental sepsis. Support or Funding Information supported by MOST and Tzu Chi Medical Center