Apelin Regulates Nuclear Factor-κB's Involvement in the Inflammatory Response of Pancreatitis.

Autor:	Han S; From the Department of Surgery, University of Texas Medical Branch, Galveston, TX., Englander EW, Gomez GA, Greeley GH Jr
Jazyk:	angličtina
Zdroj:	Pancreas [Pancreas] 2017 Jan; Vol. 46 (1), pp. 64-70.
DOI:	10.1097/MPA.0000000000000740
Abstrakt:	Objectives: Inflammation plays a key role in pancreatitis. Earlier studies from our laboratory showed that experimental pancreatitis activated the pancreatic apelin-APJ axis robustly in mice. Apelin signaling reduced neutrophil invasion and the activation of pancreatic nuclear factor (NF)-κB in mice with experimental pancreatitis. Methods: The aim of this study was to assess whether apelin-induced inhibition of pancreatic NF-κB activation was linked mechanistically to apelin's inhibition of pancreatic inflammatory mediator up-regulation in mice with cerulein-induced chronic pancreatitis (CP). Whether apelin's inhibitory effects were associated with the inhibition of NF-κB binding to the promoter region of IL-1β was examined. The effects of apelin exposure on pancreatic IκB degradation/replenishment and membrane levels of phosphorylated protein kinase C were measured. Results: Results demonstrated that apelin inhibited the up-regulation of pancreatic tumor necrosis factor α, macrophage inflammatory protein-1 α/β, and IL-1β expression significantly in mice with CP. Chromatin immunoprecipitation assay findings showed that apelin inhibited NF-κB binding to a putative NF-κB binding site in the IL-1β promoter. Apelin exposure reduced the pancreatic membrane levels of phosphorylated protein kinase C-δ and enhanced the replenishment of pancreatic IκB proteins. Conclusions: Together, these findings indicated that the inhibition of NF-κB activation by apelin was a mechanism behind the reduced pancreatic levels of inflammatory mediators in CP mice exposed to apelin.
Databáze:	MEDLINE
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