IL-1beta and IFN-gamma induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

Diabetologia. 2003 Feb;46(2):255-66. doi: 10.1007/s00125-002-1017-0. Epub 2003 Feb 12.


Aims/hypothesis: Cytokines and chemokines are important mediators of immune responses due to their ability to recruit and activate leukocytes. Using microarray analysis we observed that rat beta cells exposed to IL-1beta and IFN-gamma have increased mRNA levels of chemokines and IL-15. The aim of this study was to characterize the expression of IP-10, MIP-3alpha, fractalkine and IL-15 in rat beta cells, human pancreatic islets, and in islets isolated from NOD mice, both during the pre-diabetic period and following islet transplantation.

Methods: FACS-purified rat beta cells and human islets were cultured with IL-1beta, IFN-gamma and/or TNF-alpha. Islets were isolated from NOD or BALB/c mice at different ages. For syngeneic islet transplantation, 2- or 3-week-old NOD islets were grafted under the kidney capsule of spontaneously diabetic NOD recipients. Chemokine and IL-15 mRNA expression and protein release were evaluated, respectively, by RT-PCR and ELISA.

Results: Human islets and rat beta cells express IP-10, MIP-3alpha, fractalkine and IL-15 mRNAs upon exposure to cytokines. The expression of IL-15, IP-10 and fractalkine is regulated by IFN-gamma, while the expression of MIP-3alpha is IL-1beta-dependent. Moreover, cytokines induced IL-15, IP-10, Mig, I-TAC and MIP-3alpha protein accumulation in culture medium from human islets. In vivo, there was an age-related increase in IL-15, IP-10 and MIP-3alpha expression in islets isolated from NOD mice. Following syngeneic islet transplantation, increased expression of IL-1beta, IFN-gamma, fractalkine, IP-10, MCP-1 and MIP-3alpha mRNAs were observed in the grafts.

Conclusion/interpretation: Cytokine-exposed islets or beta cells express chemokines and IL-15. This could contribute to the recruitment and activation of mononuclear cells and development of insulitis in early Type 1 diabetes and during graft destruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Chemokine CCL20
  • Chemokine CX3CL1
  • Chemokine CXCL10
  • Chemokines / metabolism*
  • Chemokines, CC / genetics
  • Chemokines, CX3C / genetics
  • Chemokines, CXC / genetics
  • Humans
  • Interferon-gamma / pharmacology*
  • Interleukin-1 / pharmacology*
  • Interleukin-15 / genetics
  • Interleukin-15 / metabolism*
  • Islets of Langerhans / metabolism*
  • Macrophage Inflammatory Proteins / genetics
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar


  • CCL20 protein, human
  • CX3CL1 protein, human
  • Chemokine CCL20
  • Chemokine CX3CL1
  • Chemokine CXCL10
  • Chemokines
  • Chemokines, CC
  • Chemokines, CX3C
  • Chemokines, CXC
  • Cx3cl1 protein, mouse
  • Cx3cl1 protein, rat
  • Interleukin-1
  • Interleukin-15
  • Macrophage Inflammatory Proteins
  • Membrane Proteins
  • RNA, Messenger
  • Interferon-gamma