INTERLEUKIN 1β, TUMOUR NECROSIS FACTOR-α AND INTERLEUKIN 1 RECEPTOR ANTAGONIST IN NEWLY DIAGNOSED INSULIN-DEPENDENT DIABETES MELLITUS: COMPARISON TO LONG-STANDING DIABETES AND HEALTHY INDIVIDUALS

Netea, M.G.; Hâncu, Nicolae; Blok, W.L.; Grigorescu-Sido, Paula; Popa, L; Popa, Victor; Meer, J.W.M. van der

doi:10.1006/cyto.1996.0165

Cited by 37 publications

(24 citation statements)

References 13 publications

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“…For instance, the inflammatory cytokines, including IL-1β, are well-known inducers of type 1 diabetes, and high levels of IL-1β are detected in newly diagnosed type 1 diabetic patients (51,52). Numerous studies have also shown that STZ, which is an antibiotic originally isolated from Streptomyces achromogenes and an N-acetyl-glucosamine analog, is cytotoxic to pancreatic β-cells after being transported through glucose transporter 2 (53) and is used to generate type 1 diabetes model animals (54).…”

Section: Discussionmentioning

confidence: 99%

Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity

Kim

Park

Kim³

et al. 2013

International Journal of Molecular Medicine

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Abstract. Excessive and/or long-term glucocorticoid therapy reduces β-cell mass and induces hyperglycemia, which contribute to the development of steroid-induced diabetes. Ceriporia (C.) lacerata is one of the white-rot fungi and has been used in bioremediations, such as lignocellulose degradation, in nature. The pharmacologic effect of C. lacerata on steroid-induced β-cell toxicity is not known. In this study, we evaluated the effect of a crude extract from a submerged cultivation of C. lacerata on the survival and apoptosis of INS-1 rat insulin-secreting cells exposed to dexamethasone (Dex), a synthetic diabetogenic glucocorticoid. Treatment with the C. lacerata crude extract (CLCE) largely blocked the Dex-induced reduction in survival and apoptosis of INS-1 cells. Moreover, CLCE treatment inhibited Dex-induced protein kinase B (PKB) dephosphorylation without affecting Dex-induced extracellular signal-regulated protein kinase-1/2 dephosphorylation and MKP-1 upregulation. Importantly, the protective effect of CLCE on Dex-induced cytotoxicity in INS-1 cells was attenuated by LY294002, an inhibitor of PI3K/PKB. CLCE treatment, however, did not protect the INS-1 cells from the cytotoxic effects triggered by other insults, such as interleukin-1β (an inflammatory cytokine), streptozotocin (a diabetogenic drug), thapsigargin (a calcium mobilizing agent), and tunicamycin (an ER stress inducer).Collectively, these findings demonstrate for the first time the ability of CLCE to specifically protect INS-1 cells from Dex-induced cytotoxicity through the modulation of the PI3K/ PKB pathway. It is suggested that CLCE may be applied for the prevention and/or treatment of steroid diabetes in which reduction of β-cell survival and induction of β-cell apoptosis play pathogenic roles.

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Section: Discussionmentioning

confidence: 99%

Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity

Kim

Park

Kim³

et al. 2013

International Journal of Molecular Medicine

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“…This includes elevated IL-1 family members in patient cohorts before and after disease onset (31–35). Here, ELISA analysis was unable to detect differences in IL-1β/-α levels between DR lyp/lyp , DR+/+ or BN rat sera.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Serum-Induced Transcriptional Signature Associated With Type 1 Diabetes in the BioBreeding Rat

et al. 2010

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OBJECTIVEInflammatory mediators associated with type 1 diabetes are dilute and difficult to measure in the periphery, necessitating development of more sensitive and informative biomarkers for studying diabetogenic mechanisms, assessing preonset risk, and monitoring therapeutic interventions.RESEARCH DESIGN AND METHODSWe previously utilized a novel bioassay in which human type 1 diabetes sera were used to induce a disease-specific transcriptional signature in unrelated, healthy peripheral blood mononuclear cells (PBMCs). Here, we apply this strategy to investigate the inflammatory state associated with type 1 diabetes in biobreeding (BB) rats.RESULTSConsistent with their common susceptibility, sera of both spontaneously diabetic BB DRlyp/lyp and diabetes inducible BB DR+/+ rats induced transcription of cytokines, immune receptors, and signaling molecules in PBMCs of healthy donor rats compared with control sera. Like the human type 1 diabetes signature, the DRlyp/lyp signature, which is associated with progression to diabetes, was differentiated from that of the DR+/+ by induction of many interleukin (IL)-1–regulated genes. Supplementing cultures with an IL-1 receptor antagonist (IL-1Ra) modulated the DRlyp/lyp signature (P < 10−6), while administration of IL-1Ra to DRlyp/lyp rats delayed onset (P = 0.007), and sera of treated animals did not induce the characteristic signature. Consistent with the presence of immunoregulatory cells in DR+/+ rats was induction of a signature possessing negative regulators of transcription and inflammation.CONCLUSIONSParalleling our human studies, serum signatures in BB rats reflect processes associated with progression to type 1 diabetes. Furthermore, these studies support the potential utility of this approach to detect changes in the inflammatory state during therapeutic intervention.

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“…The efficacy of IL-1Ra to abrogate the effects of IL-1b was demonstrated in a variety of in vitro systems and in animal models of inflammatory diseases (21). Furthermore, an imbalance between IL-1Ra and IL-1b plays a key role in pathophysiology of chronic disorders like inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

A Bovine Whey Protein Extract Stimulates Human Neutrophils to Generate Bioactive IL-1Ra through a NF-κB- and MAPK-Dependent Mechanism

Rusu¹,

Drouin²,

Pouliot

et al. 2010

The Journal of Nutrition

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Innate immunity depends on the efficiency of neutrophils to be activated rapidly to restore homeostasis. It can benefit from priming agents that enhance neutrophil capacity to respond more efficiently to a subsequent stimulation. Among natural products, a bovine whey protein extract (WPE) has been shown to prime normal human blood neutrophils by enhancing their chemotaxis, phagocytosis, oxidative burst, and degranulation. These leukocytes are also an important source of cytokines, some of which have antiinflammatory functions. We investigated the role of WPE, as well as its mechanisms of action, on the production of interleukin (IL)-1 receptor antagonist (IL-1Ra) by neutrophils in vitro. WPE dose-dependently stimulated de novo synthesis and release of IL-1Ra by normal human blood neutrophils. Among the major proteins present in WPE, beta-lactoglobulin (beta-LG) and alpha-lactalbumin (alpha-LA) were the only active components. They had additive effects that exactly reproduced those of WPE. Similarly to WPE, they also stimulated the accumulation of IL-1beta, IL-8, IL-6, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and tumor necrosis factor-alpha. However, neutrophils incubated with WPE, beta-LG, and alpha-LA produced IL-1Ra in excess of IL-1beta and the ratio IL-1Ra:IL-1beta increased linearly. The amounts of IL-1Ra stimulated by WPE or beta-LG + alpha-LA significantly reduced the IL-1 activity in EL4 cells. Inhibitors of p38 and extracellular signal-regulated kinases (ERK)1/2 mitogen-activated protein kinase, and nuclear factor-kappaB cascades reduced neutrophil production of IL-1Ra. Our data suggest that WPE, through beta-LG + alpha-LA, has immunomodulatory properties and the potential to increase host defenses.

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INTERLEUKIN 1β, TUMOUR NECROSIS FACTOR-α AND INTERLEUKIN 1 RECEPTOR ANTAGONIST IN NEWLY DIAGNOSED INSULIN-DEPENDENT DIABETES MELLITUS: COMPARISON TO LONG-STANDING DIABETES AND HEALTHY INDIVIDUALS

Cited by 37 publications

References 13 publications

Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity

Crude extract of Ceriporia lacerata has a protective effect on dexamethasone-induced cytotoxicity in INS-1 cells via the modulation of PI3K/PKB activity

Identification of a Serum-Induced Transcriptional Signature Associated With Type 1 Diabetes in the BioBreeding Rat

A Bovine Whey Protein Extract Stimulates Human Neutrophils to Generate Bioactive IL-1Ra through a NF-κB- and MAPK-Dependent Mechanism

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