PMID- 10903798
OWN - NLM
STAT- MEDLINE
DCOM- 20000925
LR  - 20181217
IS  - 1148-5493 (Print)
IS  - 1148-5493 (Linking)
VI  - 11
IP  - 2
DP  - 2000 Jun
TI  - Interleukin-18 mRNA, but not interleukin-18 receptor mRNA, is constitutively 
      expressed in islet beta-cells and up-regulated by interferon-gamma.
PG  - 193-205
AB  - Interleukin-18 (IL-18) mRNA is expressed in islets of NOD mice during the early 
      stages of insulitis and IL-18 has therefore been implicated as a contributing 
      factor in immune-mediated beta-cell destruction. However, a recent study failed 
      to show any effect of human IL-18 on the function of isolated rat islets. Since 
      species differences have been shown between human and murine IL-18, the aims of 
      this study were to investigate 1) if species homologous IL-18 alone or following 
      IL-12 pre-exposure affected rat islet function, 2) if IL-18 dose-dependently 
      modulated IL-1 beta or interferon-gamma (IFN-gamma) + tumor necrosis factor-alpha 
      (TNF-alpha) actions on islet function, and 3) if IL-18 and IL-18 receptor 
      (IL-18R) were expressed in rat islet beta-cells. Insulin release and nitric oxide 
      (NO) production from isolated rat islets were measured after incubation with or 
      without cytokines. RT-PCR was used to quantitate mRNA expression of IL-18 and the 
      IL-18R signaling chain (IL-18R beta). There were no significant effects of 
      0.625-10 nM recombinant murine (rm) IL-18 alone on accumulated or 
      glucose-challenged insulin release or NO production after 24 hours. Fifteen pg/ml 
      of recombinant human (rh) IL-1 beta as well as 200 U/ml recombinant rat (rr) 
      IFN-gamma + 250 U/ml rhTNF-alpha significantly increased islet NO production and 
      inhibited both accumulated and glucose-challenged islet insulin release. However, 
      rmIL-18 failed to modulate these effects of IL-1 beta or IFN-gamma + TNF-alpha. 
      Although IL-12 induces IL-18R expression in Th1 and B lymphocytes, 24-hours 
      rmIL-12 preincubation neither sensitized islets to effects of 10 nM of rm or 
      rrIL-18 alone nor primed the islets to IL-1 beta actions on insulin release and 
      NO production. IL-18R beta mRNA, which was expressed in human peripheral blood 
      mononuclear cells (PBMC), was not expressed in rat insulinoma (RIN) cells or in 
      isolated rat islets, even after exposure to IL-1 beta and/or IFN-gamma + 
      TNF-alpha or IL-12. IL-18 mRNA was constitutively expressed in RIN cells, in 
      FACS-purified rat beta-cells and in intact rat and mouse islets, and was 
      up-regulated by IFN-gamma in an interferon regulatory factor-1- IRF-1) and NO - 
      independent manner. However, IL-18 protein was undetectable in lysates and 
      supernates of RIN cells by ECL, Western blotting and immunoprecipitation. In 
      conclusion, we show for the first time that IL-18 but not IL-18R is expressed in 
      rodent islet beta-cells. The physiological importance and pathological role of 
      IL-18 originating from islet beta-cells deserve further investigation.
FAU - Hong, T P
AU  - Hong TP
AD  - Steno Diabetes Center, Gentofte, Denmark.
FAU - Andersen, N A
AU  - Andersen NA
FAU - Nielsen, K
AU  - Nielsen K
FAU - Karlsen, A E
AU  - Karlsen AE
FAU - Fantuzzi, G
AU  - Fantuzzi G
FAU - Eizirik, D L
AU  - Eizirik DL
FAU - Dinarello, C A
AU  - Dinarello CA
FAU - Mandrup-Poulsen, T
AU  - Mandrup-Poulsen T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur Cytokine Netw
JT  - European cytokine network
JID - 9100879
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (IL18R1 protein, human)
RN  - 0 (IRF1 protein, human)
RN  - 0 (Il18r1 protein, mouse)
RN  - 0 (Insulin)
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-18 Receptor alpha Subunit)
RN  - 0 (Irf1 protein, mouse)
RN  - 0 (Irf1 protein, rat)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-18)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - DNA Primers/genetics
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Diabetes Mellitus, Type 1/etiology/genetics/immunology
MH  - Gene Expression
MH  - Humans
MH  - In Vitro Techniques
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Interferon Regulatory Factor-1
MH  - Interferon-gamma/*pharmacology
MH  - Interleukin-1/pharmacology
MH  - Interleukin-18/*genetics/pharmacology
MH  - Interleukin-18 Receptor alpha Subunit
MH  - Islets of Langerhans/*drug effects/*immunology/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide/biosynthesis
MH  - Phosphoproteins/genetics/metabolism
MH  - RNA, Messenger/*genetics/*metabolism
MH  - Rats
MH  - Rats, Inbred WF
MH  - Receptors, Interleukin/*genetics
MH  - Receptors, Interleukin-18
MH  - Recombinant Proteins
MH  - Tumor Necrosis Factor-alpha/pharmacology
MH  - Up-Regulation/drug effects
EDAT- 2000/07/21 11:00
MHDA- 2000/09/30 11:01
CRDT- 2000/07/21 11:00
PHST- 2000/07/21 11:00 [pubmed]
PHST- 2000/09/30 11:01 [medline]
PHST- 2000/07/21 11:00 [entrez]
PST - ppublish
SO  - Eur Cytokine Netw. 2000 Jun;11(2):193-205.