title: C-peptide reduces pro-inflammatory cytokine secretion in LPS-stimulated U937 monocytes in condition of hyperglycemia.
abstract: OBJECTIVE
  We investigated C-peptide effects on inflammatory cytokine release and adhesion of monocytes exposed to high glucose and lipopolysaccharide (LPS) in vitro.
  
  
  METHODS
  Monocytic cells (U-937) were cultured in the presence of 30 mmol/L glucose and stimulated with 0.5 ng/μL LPS in the presence or absence of C-peptide (1 μmol/L) for 24 h to induce inflammatory cytokine secretion. Adhesion of U-937 monocytes to human aortic endothelial cells (HAEC) was also studied in the presence or absence of C-peptide. Concentrations of IL-6, IL-8, macrophage inflammatory protein(MIP)-1α, and MIP-1β in supernatants from LPS-stimulated U-937 monocytes were assessed by Luminex. To gain insights into potential intracellular signaling pathways affected by C-peptide, we investigated nuclear translocation of nuclear factor(NF)-κB p65/p50 subunits by western blot in LPS-treated U-937 cells. The effect of C-peptide on LPS-induced phosphorylation of the cytoplasmic protein IκB-α was also investigated by immunoblotting.
  
  
  RESULTS
  Addition of C-peptide significantly reduced cytokine secretion from LPS-stimulated U-937 monocytes. Adhesion of U-937 cells to HAEC was also significantly reduced by C-peptide. These effects were accompanied by reduced NF-κB p65/p50 nuclear translocation and decreased phosphorylation of IκB-α.
  
  
  CONCLUSIONS
  We conclude that, in conditions of hyperglycemia, C-peptide reduces monocytes activation via inhibition of the NF-κB pathway.
authors.affiliation: Division of Immunogenetics, Department of Pediatrics, Rangos Research Center, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224, USA. jhaidet@chmca.org
authors.forename: Jaime
authors.initials: J
authors.lastname: Haidet
authors.forename: Vincenza
authors.initials: V
authors.lastname: Cifarelli
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
authors.forename: Patrizia
authors.initials: P
authors.lastname: Luppi
mesh_terms: D001011:Aorta / Q000166:cytology; D002096:C-Peptide / Q000737:chemistry / Q000494:pharmacology*; D054405:Chemokine CCL3 / Q000378:metabolism; D054407:Chemokine CCL4 / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology; D010766:Phosphorylation; D020298:U937 Cells
chemical_list: D002096:C-Peptide; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides