A functional CD40 receptor is expressed in pancreatic beta cells

Diabetes Research Institute, University of Miami, كورال غيبلز، فلوريدا, Florida, United States
Diabetologia (Impact Factor: 6.67). 03/2005; 48(2):268-76. DOI: 10.1007/s00125-004-1645-7
Source: PubMed


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.
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.
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.
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.

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    • "CD40 contributes not only to physiological cell-mediated responses, but also to immune pathological conditions such as autoimmune and vascular diseases, leading to a chronic inflammatory state. It has been previously reported that the CD40 molecule is expressed also in human pancreatic beta-cells and that expression can be upregulated by incubation with a cocktail of proinflammatory cytokines (Klein et al., 2005). CD40 signals in beta-cells upregulate secretion of interleukin (IL)- 6, IL-8, macrophage inflammatory protein (MIP)-1, and MIP-1β (Barbé-Tuana et al., 2006). "

    Full-text · Chapter · Nov 2011
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    • "Such attempts include the blockade of the CD40-CD40L costimulatory pathway deemed to be crucial to the activation and differentiation of T effector cells. Because CD40 is expressed by pancreatic islet cells (8), blockade of this pathway may be particularly relevant (6–12). "
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