A functional CD40 receptor is expressed in pancreatic beta cells

D. Klein, F. Barbé-Tuana, Alberto Pugliese, H. Ichii, D. Garza, M. Gonzalez, Ruth Molano, Camillo Ricordi, Ricardo Pastori

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Aims/hypothesis: 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-1β, IFN-γ and TNF-α). CD40 signalling in NIT-1 insulinoma cells activates nuclear factor kappa-B, demonstrating that CD40 is functional. Conclusions/interpretation: 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-κB. 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.

Original languageEnglish
Pages (from-to)268-276
Number of pages9
JournalDiabetologia
Volume48
Issue number2
DOIs
StatePublished - Feb 1 2005

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Insulin-Secreting Cells
Islets of Langerhans
Insulinoma
Neurons
Islets of Langerhans Transplantation
NF-kappa B
Tumor Necrosis Factor Receptors
Luciferases
Reverse Transcriptase Polymerase Chain Reaction
Autoimmunity
Interleukin-1
Reporter Genes
Cell Survival
Flow Cytometry
Western Blotting
Immunohistochemistry
Cytokines
Antibodies
Proteins

Keywords

  • Beta cells
  • CD40
  • Diabetes mellitus
  • Islets
  • NIT-1
  • Nuclear factor kappa-B

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

A functional CD40 receptor is expressed in pancreatic beta cells. / Klein, D.; Barbé-Tuana, F.; Pugliese, Alberto; Ichii, H.; Garza, D.; Gonzalez, M.; Molano, Ruth; Ricordi, Camillo; Pastori, Ricardo.

In: Diabetologia, Vol. 48, No. 2, 01.02.2005, p. 268-276.

Research output: Contribution to journalArticle

Klein, D, Barbé-Tuana, F, Pugliese, A, Ichii, H, Garza, D, Gonzalez, M, Molano, R, Ricordi, C & Pastori, R 2005, 'A functional CD40 receptor is expressed in pancreatic beta cells', Diabetologia, vol. 48, no. 2, pp. 268-276. https://doi.org/10.1007/s00125-004-1645-7
Klein D, Barbé-Tuana F, Pugliese A, Ichii H, Garza D, Gonzalez M et al. A functional CD40 receptor is expressed in pancreatic beta cells. Diabetologia. 2005 Feb 1;48(2):268-276. https://doi.org/10.1007/s00125-004-1645-7
Klein, D. ; Barbé-Tuana, F. ; Pugliese, Alberto ; Ichii, H. ; Garza, D. ; Gonzalez, M. ; Molano, Ruth ; Ricordi, Camillo ; Pastori, Ricardo. / A functional CD40 receptor is expressed in pancreatic beta cells. In: Diabetologia. 2005 ; Vol. 48, No. 2. pp. 268-276.
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