title: Apelin Regulates Nuclear Factor-κB's Involvement in the Inflammatory Response of Pancreatitis.
abstract: 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.
  
  
  
  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 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.
  
  
  
  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.
authors.affiliation: From the Department of Surgery, University of Texas Medical Branch, Galveston, TX.
authors.forename: Song
authors.initials: S
authors.lastname: Han
authors.forename: Ella W
authors.initials: EW
authors.lastname: Englander
authors.forename: Guillermo A
authors.initials: GA
authors.lastname: Gomez
authors.forename: George H
authors.initials: GH
authors.lastname: Greeley
mesh_terms: D000818:Animals; D000073861:Apelin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002108:Ceruletide; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism*; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000073861:Apelin; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002108:Ceruletide