BACKGROUND: The onset of @entity656 ( @entity656 ) is characterized by early protease activation followed by @entity32 and organ damage, but the mechanisms are poorly understood. AIMS: We hypothesized that histone deacetylase (HDAC) inhibition might exert protective effects on @entity656 and investigated the role of HDAC in trypsin activation, @entity32 , and tissue damage in severe @entity656 . METHODS: Male C57Bl/6 @entity19 were treated i.p. with the HDAC inhibitor @entity3996 (2  mg/kg) prior to retrograde infusion of @entity7362 (5  %) into the pancreatic duct. Serum levels of amylase and @entity777 , pancreatic levels of @entity9701 ( @entity9701 ) as well as tissue morphology and myeloperoxidase activity in the pancreas and lung were determined 24  h after @entity7362 challenge. Trypsin activation was analyzed in isolated acinar cells. Quantitative RT-PCR was used to examine the expression of pro-inflammatory mediators in the pancreas. RESULTS: Pretreatment with @entity3996 decreased amylase levels by 70  % and protected against tissue @entity130 . Moreover, HDAC inhibition reduced systemic @entity777 by more than 95  % and pulmonary myeloperoxidase activity by 75  %. Notably, inhibition of HDAC abolished @entity7362 -induced gene expression of @entity1996 , @entity9701 , @entity1750 , @entity777 , and @entity635 in the pancreas. In addition, HDAC inhibition reduced @entity8629 -induced trypsinogen activation in isolated acinar cells. CONCLUSION: Our findings show that HDAC regulates trypsin activation, @entity32 , and tissue damage in @entity656 . Thus, targeting HDAC could serve as novel therapeutic approach in the management of severe @entity656 .

Histone Deacetylase Regulates Trypsin Activation, Inflammation, and Tissue Damage in Acute Pancreatitis in XXXX .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity7362 :: ('MESH:D013656', 'Chemical') :: ['taurocholic acid', 'taurocholate'] @entity656 :: ('MESH:D019283', 'Disease') :: ['AP', 'acute pancreatitis'] @entity1750 :: ('20296(Tax:10090)', 'Gene') :: ['monocyte chemotactic protein-1'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity635 :: ('16176(Tax:10090)', 'Gene') :: ['IL-1b'] @entity3996 :: ('MESH:C012589', 'Chemical') :: ['trichostatin A'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['interleukin (IL)-6', 'IL-6'] @entity9701 :: ('20310(Tax:10090)', 'Gene') :: ['MIP-2', 'macrophage inflammatory protein-2'] @entity8629 :: ('MESH:D002108', 'Chemical') :: ['cerulein'] @entity1996 :: ('19225(Tax:10090)', 'Gene') :: ['cyclooxygenase-2'] @entity130 :: ('MESH:D014947', 'Disease') :: ['injury in the pancreas']
@entity19 :: (10090,Species) :: ['Mice']
