A functional CD40 receptor is expressed in pancreatic beta cells.
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.
Klein
D
D
Diabetes Research Institute, University of Miami School of Medicine, 1450 NW 10th Avenue, Miami, FL 33136, USA.
Barbé-Tuana
F
F
Pugliese
A
A
Ichii
H
H
Garza
D
D
Gonzalez
M
M
Molano
R D
RD
Ricordi
C
C
Pastori
R L
RL
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
D015703:Antigens, CD; D019013:CD40 Antigens; D017931:DNA Primers; D018076:DNA, Complementary; D016328:NF-kappa B; D012333:RNA, Messenger; D008156:Luciferases