Functional IL-18 Is produced by primary pancreatic mouse islets and NIT-1 beta cells and participates in the progression towards destructive insulitis.
BACKGROUND
Preclinical stages of type 1 diabetes are characterized by infiltrating T cells and by the peri- and intra-islet accumulation of pro-inflammatory mediators, such as IFNgamma.


RESULTS
Using quantitative PCR we demonstrated that mRNA specific for the IFNgamma-inducing cytokine IL-18 is upregulated in NIT-1 beta cells and intact mouse islets upon exposure to IL-1beta, IFNgamma and TNFalpha. The biological activity of IL-18 was blocked using caspase inhibitors and anti-IL-18 antibodies. Increased IL-18 expression was also detected in islets during advanced stages of insulitis and correlated with elevated transcripts for IFNgamma and for the IL-18 receptor.


CONCLUSIONS
Thus, beta cells produce bioactive IL-18 in the course of insulitis and actively contribute to the exacerbation of inflammation leading to their own demise.
Frigerio
Simona
S
University Children's Hospital, and Department of Clinical and Biological Science, Basel, Switzerland.
Holländer
Georg A
GA
Zumsteg
Urs
U
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D018450:Disease Progression; D005786:Gene Expression Regulation; D020382:Interleukin-18 / Q000235:genetics* / Q000502:physiology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D008815:Mice, Inbred Strains; D010182:Pancreatic Diseases / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
D017931:DNA Primers; D020382:Interleukin-18; D012333:RNA, Messenger