title: A functional CD40 receptor is expressed in pancreatic beta cells.
abstract: OBJECTIVE
  Despite differences in function and embryonic origin, pancreatic islet cells and neurons express proteins belonging to the tumour necrosis factor receptor superfamily. While neurons express the CD40 receptor, it is unknown whether islet cells also express it. We investigated CD40 expression in human and mouse pancreatic islets as well as in NIT-1 insulinoma cells.
  
  
  METHODS
  CD40 expression was studied by reverse transcriptase polymerase chain reaction, flow cytometry, immunohistochemistry and western blot. Responses mediated by CD40 were assessed by a luciferase gene reporter assay following stimulation with a CD40 agonist antibody.
  
  
  RESULTS
  We found that CD40 is expressed in mouse and human pancreatic islet cells. CD40 is expressed by beta cells, and its expression is upregulated by proinflammatory cytokines (IL-1beta, IFN-gamma and TNF-alpha). CD40 signalling in NIT-1 insulinoma cells activates nuclear factor kappa-B, demonstrating that CD40 is functional.
  
  
  CONCLUSIONS
  We present evidence that, in addition to immune cell types, mouse and human pancreatic beta cells express CD40. Its expression is upregulated by proinflammatory stimuli, and signalling through this receptor activates NF-kappaB. We suggest that the effects of inflammatory stimuli that affect beta cell function and survival may be also mediated by signalling through the CD40 receptor. Thus, CD40 may have a role in processes associated with islet autoimmunity and transplantation.
authors.affiliation: Diabetes Research Institute, University of Miami School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA.
authors.forename: D
authors.initials: D
authors.lastname: Klein
authors.forename: F
authors.initials: F
authors.lastname: Barbé-Tuana
authors.forename: A
authors.initials: A
authors.lastname: Pugliese
authors.forename: H
authors.initials: H
authors.lastname: Ichii
authors.forename: D
authors.initials: D
authors.lastname: Garza
authors.forename: M
authors.initials: M
authors.lastname: Gonzalez
authors.forename: R D
authors.initials: RD
authors.lastname: Molano
authors.forename: C
authors.initials: C
authors.lastname: Ricordi
authors.forename: R L
authors.initials: RL
authors.lastname: Pastori
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D019013:CD40 Antigens / Q000235:genetics* / Q000276:immunology; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D017930:Genes, Reporter; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016328:NF-kappa B / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D015703:Antigens, CD; D019013:CD40 Antigens; D017931:DNA Primers; D018076:DNA, Complementary; D016328:NF-kappa B; D012333:RNA, Messenger; D008156:Luciferases