Selective inhibition of XXXX attenuates the severity of cerulein-induced acute pancreatitis.

@entity32 @entity1991 @entity656 @entity548 @entity19 @entity651 @entity8586 @entity358 @entity10873
BACKGROUND: @entity656 ( @entity656 ) is associated with increased cytokine production, which can ultimately produce deleterious local and systemic effects. The transcription factor @entity1991 is activated by degradation of its inhibitory factor, IkappaB, and can stimulate various cytokines. The purpose of this study was to determine whether the inhibition of @entity1991 binding activity with a novel peptide that binds to the @entity1991 essential modifier binding domain (NBD) could attenuate the severity of @entity656 . STUDY DESIGN: @entity656 was induced in Swiss Webster @entity19 by hourly injections of the @entity8586 analogue cerulein (50 microg/kg). @entity19 were injected with either the wild-type or control (mutated) NBD peptide at the time of the first cerulein injection; they were then sacrificed over a time course, and pancreata and lungs were harvested for histologic analysis and scoring. @entity10873 activity was measured to assess neutrophil sequestration as an indicator of @entity32 . @entity1991 binding activity and steady-state levels of IkappaB and @entity1991 subunits were determined by gel shift and Western blot, respectively. RESULTS: @entity656 resulted in increased @entity1991 DNA-binding activity and decreased steady-state levels of IkappaB. Treatment with NBD peptide decreased @entity32 in the pancreas, decreased @entity548 in the lungs, and decreased @entity10873 activity in both @entity358 . CONCLUSIONS: The marked induction of @entity1991 binding activity suggests a role for this transcription factor in the early inflammatory changes associated with @entity656 . Treatment with the NBD peptide attenuated the severity of injury associated with @entity656 . Novel compounds that selectively target @entity1991 may prove to be useful treatment of @entity656 and @entity656 -associated @entity651 .
