A natural interleukin 1 (IL-1) inhibitor counteracts the inhibitory effect of IL-1 on insulin production in cultured rat pancreatic islets

Dayer-Métroz, Marie-Dominique; Wollheim, Claes B.; Seckinger, P; Dayer, Jean‐Michel

doi:10.1016/0896-8411(89)90152-2

Cited by 54 publications

(20 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Values after 3 days exposure to IL-1β (50 U/ml) and IFN-γ (1,000 U/ml) were determined by ELISA and with Griess reagent protocol respectively, and are expressed as means±SEM from three to four independent experiments. One superscript symbol p≤0.05, two superscript symbols p≤0.01; three superscript symbols p≤0.001, four superscript symbols p≤0.0001: ( †) compared with control C57BL/6 islets (under similar conditions); (*) compared with control C57BL/6 islets (no cytokines added); ( ‡) compared with Irf-1 −/− islets (no cytokines added) only minor effects on cell viability [6,38]; they also show that blocking IL-1β action with IL-1Ra can prevent the deleterious effects [24,34,[39][40][41][42]. Although this was confirmed in our study, we observed abnormal glucosestimulated insulin release from Irf-1 −/− islets under basal conditions that could not be corrected by IL-1Ra, indicating an independent defect in beta cell secretory machinery of Irf-1 −/− islets.…”

Section: Discussionmentioning

confidence: 93%

Interferon regulatory factor-1 is a key transcription factor in murine beta cells under immune attack

Gysemans¹,

Callewaert²,

Moore

et al. 2009

Diabetologia

View full text Add to dashboard Cite

Aims/hypothesis IFN-γ, together with other inflammatory cytokines such as IL-1β and TNF-α, contributes to beta cell death in type 1 diabetes. We analysed the role of the transcription factor interferon regulatory factor (IRF)-1, a downstream target of IFN-γ/signal transducer and activator of transcription (STAT)-1, in immune-mediated beta cell destruction. Methods Islets from mice lacking Irf-1 (Irf-1 −/− ) and control C57BL/6 mice were transplanted in overtly diabetic NOD mice. Viability and functionality of islets were evaluated in vitro. Chemokine expression by Irf-1 −/− islets and INS-1E cells transfected with Irf-1 short interfering RNA (siRNA) was measured by real-time PCR as well as in functional assays in vitro. Results IRF-1 deletion in islets was associated with higher prevalence of primary non-function (63% vs 25%, p≤0.05) and shorter functioning graft survival (6.0±2.6 vs 10.4± 4.8 days, p≤0.05) in contrast to similar skin graft survival. Although Irf-1 −/− islets were resistant to cytokine-induced cell death, insulin secretion by them was lower than that of control C57BL/6 islets under medium and cytokine conditions. IL-1 receptor antagonist partly restored the cytokine-induced secretory defect in vitro and completely prevented primary non-function in vivo. Cytokine-exposed Irf-1 −/− islets and INS-1E cells transfected with Irf-1 siRNA showed increased expression of Mcp-1 (also known as Ccl2), Ip-10 (also known as Cxcl10), Mip-3α (also known as Ccl20) and Inos (also known as Nos2) mRNA and elevated production of monocyte chemoattractant protein-1 (MCP-1) and nitrite compared with controls. In vivo, Irf-1 −/− islets displayed a higher potential to attract immune cells, reflected by more aggressive immune infiltration in the grafted islets. Conclusions/interpretation These data indicate a key regulatory role for IRF-1 in insulin and chemokine secretion by pancreatic islets under inflammatory attack.

show abstract

Section: Discussionmentioning

confidence: 93%

Interferon regulatory factor-1 is a key transcription factor in murine beta cells under immune attack

Gysemans¹,

Callewaert²,

Moore

et al. 2009

Diabetologia

View full text Add to dashboard Cite

show abstract

“…Also, in isolated rat islets, IL-1 has been shown to promote COX-2 expression and prostaglandin E 2 (PGE 2 ) formation (35,36). Consequently, COX-2 has been proposed to play a role in the pathogenesis of type 1 diabetes (37).…”

Section: T Tabatabaie and Associatesmentioning

confidence: 99%

Free Radicals and the Pathogenesis of Type 1 Diabetes

et al. 2003

View full text Add to dashboard Cite

Free radical formation evoked by proinflammatory cytokines has been suggested to be involved in the destruction of ␤-cells in the course of type 1 diabetes development. However, there is no direct evidence to support this hypothesis. In this study, we used electron paramagnetic resonance spectroscopy in conjunction with spin-trapping methodology to directly determine whether cytokines give rise to free radical formation in the islets. Our results demonstrate that direct, in vivo administration of tumor necrosis factor-␣ (1,000 units), interleukin-1␤ (1,000 units), and interferon-␥ (2,000 units) into the rat pancreas through a bile duct cannula leads to the formation of lipid-derived free radicals in this tissue. These free radicals most likely are generated by the ␤-cells because previous depletion of these cells by streptozotocin abolished the cytokine-induced free radical formation. Furthermore, macrophage depletion was found to decrease the production of free radicals. Inhibition of the enzyme inducible cyclooxygenase (COX-2) and the transcription factor nuclear factor-B (NF-B) significantly diminished the free radicals' signal intensity, implicating these factors in the formation of free radicals. We have also demonstrated that cytokine treatment leads to the activation of NF-B in the pancreatic islets of the rats.

show abstract

“…Diabetes 51: 1772-1778, 2002 I nterleukin-1␤ (IL-1␤) and prostaglandin E 2 (PGE 2 ) both inhibit glucose-induced insulin secretion from the pancreatic islet (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). The similarity of their actions and that both are mediators of inflammation have led to a consideration of whether PGE 2 might mediate the effects of IL-1␤ to inhibit insulin secretion (7,12). Most recently it was demonstrated that two specific antagonists of cyclooxygenase (COX)-2 activity prevent IL-1␤-induced inhibition of glucose-induced insulin secretion from rat islets, and that this cytokine action could be restored by the addition of exogenous PGE 2 in the presence of the COX-2 inhibitors (13).…”

mentioning

confidence: 99%

Inhibition of Interleukin-1β-Induced COX-2 and EP3 Gene Expression by Sodium Salicylate Enhances Pancreatic Islet β-Cell Function

2002

View full text Add to dashboard Cite

Previous work has suggested that functional interrelationships may exist between inhibition of insulin secretion by interleukin (IL)-1␤ and the endogenous synthesis of prostaglandin E 2 (PGE 2 ) in the pancreatic islet. These studies were performed to ascertain the relative abundance of E prostaglandin (EP) receptor mRNAs in tissues that are major targets, or major degradative sites, of insulin; to identify which EP receptor type mediates PGE 2 inhibition of insulin secretion in pancreatic islets; and to examine possible sites of action through which sodium salicylate might affect IL-1␤/PGE 2 interactions. Real-time fluorescence-based RT-PCR indicated that EP3 is the most abundant EP receptor type in islets, liver, kidney, and epididymal fat. EP3 mRNA is the least, whereas EP2 mRNA is the most, abundant type in skeletal muscle. Misoprostol, an EP3 agonist, inhibited glucose-induced insulin secretion from islets, an event that was prevented by preincubation with pertussis toxin, by decreasing cAMP. Electromobility shift assays demonstrated that sodium salicylate inhibits IL-1␤-induced nuclear factor-B (NF-B) activation. Sodium salicylate also prevented IL-1␤ from inducing EP3 and cyclooxygenase (COX)-2 gene expression in islets and thereby prevented IL-1␤ from inhibiting glucose-induced insulin secretion. These findings indicate that the sites of action through which sodium salicylate inhibits these negative effects of IL-1␤ on ␤-cell function include activation of NF-B as well as generation of PGE 2 by COX-2.

show abstract

A natural interleukin 1 (IL-1) inhibitor counteracts the inhibitory effect of IL-1 on insulin production in cultured rat pancreatic islets

Cited by 54 publications

References 21 publications

Interferon regulatory factor-1 is a key transcription factor in murine beta cells under immune attack

Interferon regulatory factor-1 is a key transcription factor in murine beta cells under immune attack

Free Radicals and the Pathogenesis of Type 1 Diabetes

Inhibition of Interleukin-1β-Induced COX-2 and EP3 Gene Expression by Sodium Salicylate Enhances Pancreatic Islet β-Cell Function

Contact Info

Product

Resources

About