Polyethylene Glycolated Recombinant TNF Receptor I Improves Insulitis and Reduces Incidence of Spontaneous and Cyclophosphamide-Accelerated Diabetes in Nonobese Diabetic Mice

Wang, Jinlin; Qian, Xueming; Chinookoswong, Narumol; Lu, John; Chow, Gwyneth; Theill, Lars E.; Shi, Zhiqing

doi:10.1210/en.2002-220412

Cited by 12 publications

(6 citation statements)

References 38 publications

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“…Induction of the circulating IL-1 receptor antagonist and the soluble TNF␣ p55 receptor demonstrate the well-known anti-inflammatory effects of IL-6 (36). The prophylactic and therapeutic effect of the soluble TNF-␣ receptor type I, as TNF-␣ antagonist, against diabetic insulitis has already been documented in female nonobese diabetic (NOD) mice (37). Moreover, IL-6 is responsible for amelioration of local and systemic inflammation by stimulation of IL-10 production (38).…”

Section: Discussionmentioning

confidence: 99%

The −174GG Interleukin-6 Genotype Is Protective From Retinopathy and Nephropathy in Juvenile Onset Type 1 Diabetes Mellitus

et al. 2009

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ABSTRACT:The aim of our study was to determine an association between the Ϫ174GϾC IL-6 polymorphism (rs1800795) and occurrence of retinopathy and nephropathy in type 1 diabetes mellitus (T1DM) patients. Two hundred ten children/adolescents with longstanding T1DM (16.5 Ϯ 3.8 y; with diabetes duration of 8.4 Ϯ 3.0 y) were enrolled into the study. A group of 170 healthy young (16.9 Ϯ 5.2 y) sex-matched volunteers was qualified as the control. The IL-6 polymorphism was genotyped with the PCR-RFLP method. Serum and urine IL-6 concentrations were measured by the ultra-sensitive ELISA tests. The Ϫ174GG genotype was under represented in the diabetic patients compared with the controls. Patients with this genotype were free from nephropathy and retinopathy. The group of Ϫ174GG carriers was characterized by the highest urine IL-6 concentrations in relation to other genotypes. In the multivariate logistic regression analysis adjusted for age, duration of the disease, age of disease onset, HbA1c, and albumin excretion rate, the Ϫ174GG genotype was the only independent variable that significantly decreased the risk of jointly analyzed retinopathy and nephropathy [OR ϭ 0.65; 95% CI ϭ 0.52-0.82; p ϭ 0.0003]. We propose that the Ϫ174GG patients are protected from late diabetic complications by different IL-6 dependent mechanisms. (Pediatr Res 66: 341-345, 2009)

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Section: Discussionmentioning

confidence: 99%

The −174GG Interleukin-6 Genotype Is Protective From Retinopathy and Nephropathy in Juvenile Onset Type 1 Diabetes Mellitus

et al. 2009

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“…In addition, Akt has been reported to promote GSK3β phosphorylation and deactivation which indirectly favors LEF-dependent transcription (Gonzalez-Robayna et al, 2000; Fan et al, 2010). The nuclear translocation of NFκB is also promoted by Akt (Wang et al, 2002). …”

Section: Nuclear Events Controlled By Fshmentioning

confidence: 99%

Mapping the follicle-stimulating hormone-induced signaling networks

et al. 2011

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Follicle-stimulating hormone (FSH) is a central regulator of male and female reproductive function. Over the last decade, there has been a growing perception of the complexity associated with FSH-induced cellular signaling. It is now clear that the canonical Gs/cAMP/PKA pathway is not the sole mechanism that must be considered in FSH biological actions. In parallel, consistent with the emerging concept of biased agonism, several examples of ligand-mediated selective signaling pathway activation by gonadotropin receptors have been reported. In this context, it is important to gain an integrative view of the signaling pathways induced by FSH and how they interconnect to form a network. In this review, we propose a first attempt at building topological maps of various pathways known to be involved in the FSH-induced signaling network. We discuss the multiple facets of FSH-induced signaling and how they converge to the hormone integrated biological response. Despite of their incompleteness, these maps of the FSH-induced signaling network represent a first step toward gaining a system-level comprehension of this hormone’s actions, which may ultimately facilitate the discovery of novel regulatory processes and therapeutic strategies for infertility and non-steroidal contraception.

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“…The final version may differ from this version. 29 1994;Flodstrom et al, 1999;Holstad and Sandler, 2001;Suarez-Pinzon et al, 2001;Drage et al, 2002;Wang et al, 2002;Thomas et al, 2004).…”

Section: Vgx-1027 Treatment Reduces Clinical Signs Of Mld-stz-inducedmentioning

confidence: 99%

A Potent Immunomodulatory Compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxasole Acetic Acid, Prevents Spontaneous and Accelerated Forms of Autoimmune Diabetes in NOD Mice and Inhibits the Immunoinflammatory Diabetes Induced by Multiple Low Doses of Streptozotocin in CBA/H Mice

Stošić‐Grujičić¹,

Cvetković²,

Mangano³

et al. 2006

J Pharmacol Exp Ther

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(S,R)-3-Phenyl-4,5-dihydro-5-isoxasole acetic acid (VGX-1027) is an isoxazole compound that exhibits various immunomodulatory properties. The capacity of VGX-1027 to prevent interleukin (IL)-1beta plus interferon-gamma-induced pancreatic islet death in vitro prompted us to evaluate its effects on the development of autoimmune diabetes in preclinical models of human type 1 diabetes mellitus (T1D). Administration of VGX-1027 to NOD mice with spontaneous or accelerated forms of diabetes induced either by injection of cyclophosphamide or by transfer of spleen cells from acutely diabetic syngeneic donors markedly reduced the cumulative incidence of diabetes and insulitis. In addition, VGX-1027 given either i.p. or p.o. to CBA/H mice made diabetic with multiple low doses of streptozotocin successfully counteracted the development of destructive insulitis and hyperglycemia. The animals receiving VGX-1027 exhibited reduced production of the proinflammatory mediators tumor necrosis factor-alpha, IL-1beta, macrophage migration inhibitory factor, and inducible nitric-oxide synthase-mediated nitric oxide generation in both pancreatic islets and peripheral compartments. These results indicate that VGX-1027 probably exerts its antidiabetogenic effects by limiting cytokine-mediated immunoinflammatory events, leading to inflammation and destruction of pancreatic islets. VGX-1027 seems worthy of being considered as a candidate drug in the development of new therapeutic strategies for the prevention and early treatment of T1D.

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Polyethylene Glycolated Recombinant TNF Receptor I Improves Insulitis and Reduces Incidence of Spontaneous and Cyclophosphamide-Accelerated Diabetes in Nonobese Diabetic Mice

Cited by 12 publications

References 38 publications

The −174GG Interleukin-6 Genotype Is Protective From Retinopathy and Nephropathy in Juvenile Onset Type 1 Diabetes Mellitus

The −174GG Interleukin-6 Genotype Is Protective From Retinopathy and Nephropathy in Juvenile Onset Type 1 Diabetes Mellitus

Mapping the follicle-stimulating hormone-induced signaling networks

A Potent Immunomodulatory Compound, (S,R)-3-Phenyl-4,5-dihydro-5-isoxasole Acetic Acid, Prevents Spontaneous and Accelerated Forms of Autoimmune Diabetes in NOD Mice and Inhibits the Immunoinflammatory Diabetes Induced by Multiple Low Doses of Streptozotocin in CBA/H Mice

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