Administration of Silica Prevents Diabetes in BB-Rats

Oschilewski, U; Kiesel, U; Kolb, Hubert

doi:10.2337/diab.34.2.197

Cited by 130 publications

(61 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…44 -46 For example, the result that depletion of macrophages via silica particles in NOD mice or BB rats resulted in protection from diabetes was interpreted to suggest an important role for macrophages in the priming of diabetogenic T cells. 29,37,38 Another feature noted in these studies was the marked reduction in the incidence of insulitis in macrophage-depleted mice. 29,37 Other groups used clodronate-dependent elimination of macrophages in NOD mice to demonstrate protection from diabetes.…”

Section: Macrophages Kill ␤ Cells In T1dm 2143mentioning

confidence: 87%

“…29,37,38 Another feature noted in these studies was the marked reduction in the incidence of insulitis in macrophage-depleted mice. 29,37 Other groups used clodronate-dependent elimination of macrophages in NOD mice to demonstrate protection from diabetes. 34,39 Here again, young NOD mice that were depleted of macrophages were unable to generate cytotoxic T cells, thereby implicating the macrophage as an essential accessory cell for the differentiation of effector diabetogenic T cells.…”

Section: Macrophages Kill ␤ Cells In T1dm 2143mentioning

confidence: 87%

See 1 more Smart Citation

In CD4+ T-Cell-Induced Diabetes, Macrophages Are the Final Effector Cells that Mediate Islet β-Cell Killing

Calderon

Suri

Unanue

2006

The American Journal of Pathology

111

113

View full text Add to dashboard Cite

To understand better how diabetogenic CD4 ؉ T cells induce isletType 1 diabetes mellitus (T1DM) is an autoimmune disorder wherein the pancreatic islet ␤ cells are destroyed by autoreactive T cells resulting in a state of persistent hyperglycemia. The nonobese diabetic (NOD) mouse and the bio breeding (BB) rat are two attractive animal models for T1DM that follow many characteristics of the human disease including the expression of the diabetessusceptible class II major histocompatibility complex (MHC) alleles. 1-3 T1DM in both humans and rodents is characterized by distinct histopathological stages. The first stage, termed peri-insulitis, consists of an initial infiltration of leukocytes surrounding the islets without apparent effect on ␤ cells; this is followed by an aggressive phase wherein the infiltrate actively invades the islets and kills the ␤ cells, leading to diabetes. CD4 ϩ T cells are essential for development of diabetes by recognizing ␤-cell antigens in the context of the class II MHC I-A g7 . Involvement of CD8 ϩ T cells has also been extensively documented. 4 -7 Various mechanisms for inducing ␤-cell death have been proposed including a role for Fas/FasL, perforin/granzyme pathway, Rae1-NKG2D interaction, and reactive oxygen species induced by proinflammatory cytokines. 8 -12 A major hurdle in understanding the role of various leukocytes in T1DM is the large and varied time span between peri-insulitis and onset of diabetes (in NOD mice it can be anywhere between 10 to 14 weeks). Moreover, the presence of both CD4 ϩ and CD8 ϩ T cells makes it difficult to dissect the effector pathways used by each to induce islet ␤-cell death. To this end, we have examined an accelerated model of T1DM using the diabetogenic CD4 ϩ T cell, BDC2.5, expressed as a T-cell receptor (TCR) transgene in NOD mice (from here on referred to as BDC T cells). BDC T cells recognize an unidentified islet ␤-cell antigen presented by the I-A g7 class II MHC molecule of NOD mice. 13 Activated BDC T cells transfer diabetes into NOD.scid recipients in a short period of time with reproducible kinetics and incidence.

show abstract

Section: Macrophages Kill ␤ Cells In T1dm 2143mentioning

confidence: 87%

Section: Macrophages Kill ␤ Cells In T1dm 2143mentioning

confidence: 87%

In CD4+ T-Cell-Induced Diabetes, Macrophages Are the Final Effector Cells that Mediate Islet β-Cell Killing

Calderon

Suri

Unanue

2006

The American Journal of Pathology

111

113

View full text Add to dashboard Cite

show abstract

“…Macrophages are the first cells to infiltrate the islets in both NOD mice and BB rats [6,57]. Activated macrophages are toxic to pancreatic islets in vitro [58] and macrophage depletion or inactivation prevent diabetes in BB rats and NOD mice [59,60]. IP-10 was reported to attract monocytes [61], and it is therefore conceivable that the early expression of IP-10 (current data) and MCP-1 [8] by NOD islet cells contributes to the recruitment of macrophages in the early stages of insulitis.…”

Section: Discussionmentioning

confidence: 99%

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

et al. 2003

View full text Add to dashboard Cite

Aims/hypothesis. Cytokines and chemokines are important mediators of immune responses due to their ability to recruit and activate leukocytes. Using microarray analysis we observed that rat beta cells exposed to IL-1β and IFN-γ have increased mRNA levels of chemokines and IL-15. The aim of this study was to characterize the expression of IP-10, MIP-3α, fractalkine and IL-15 in rat beta cells, human pancreatic islets, and in islets isolated from NOD mice, both during the pre-diabetic period and following islet transplantation. Methods. FACS-purified rat beta cells and human islets were cultured with IL-1β, IFN-γ and/or TNF-α. Islets were isolated from NOD or BALB/c mice at different ages. For syngeneic islet transplantation, 2-or 3-week-old NOD islets were grafted under the kidney capsule of spontaneously diabetic NOD recipients. Chemokine and IL-15 mRNA expression and protein release were evaluated, respectively, by RT-PCR and ELISA.Results. Human islets and rat beta cells express IP-10, MIP-3α, fractalkine and IL-15 mRNAs upon exposure to cytokines. The expression of IL-15, IP-10 and fractalkine is regulated by IFN-γ, while the expression of MIP-3α is IL-1β-dependent. Moreover, cytokines induced IL-15, IP-10, Mig, I-TAC and MIP-3α protein accumulation in culture medium from human islets. In vivo, there was an age-related increase in IL-15, IP-10 and MIP-3α expression in islets isolated from NOD mice. Following syngeneic islet transplantation, increased expression of IL-1β, IFN-γ, fractalkine, IP-10, MCP-1 and MIP-3α mRNAs were observed in the grafts. Conclusion/interpretation. Cytokine-exposed islets or beta cells express chemokines and IL-15. This could contribute to the recruitment and activation of mononuclear cells and development of insulitis in early Type 1 diabetes and during graft destruction. [Diabetologia (2003) 46:255-266] Keywords Type 1 diabetes mellitus, chemokines, IL-15, NOD mice, beta cells, interferon-γ, interleukin-1β, pancreatic islets, islet transplantation, insulitis.

show abstract

“…Macrophages have been repeatedly shown to play a crucial role in early phases of disease development in animal models: they constitute the major infiltrating cell type during early insulitis in BB rats [1], NOD mice [2] and low-dose streptozotocintreated mice [3]. Impairment of maerophage function prevents disease manifestation in these animals [3][4][5]. Activated but not resident macrophages were found to rapidly and effectively kill islet ceils but not hepatocytes or thyroeytes [6].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic action of IL‐1β against pancreatic islets is mediated via nitric oxide formation and is inhibited by N^G‐monomethyl‐l‐arginine

et al. 1992

View full text Add to dashboard Cite

IL.I,3 has been previously shown to act as a cytotoxic agent in islets. Here we show by electron microscopy of al$inate encapsulated islets, that islet cell lysis is induced by culturing islets for 24 or 48 h in the presence of IL.I~. The extent of lysis depends on the IL-1,6 concentration and is slightly enhanced by the addition of TNF-g. Calls can be protected from lysis by N°-monomethyl-L-arginine. Lysis is paralleled by an increase in nitrite concentration in culture supernatants of whole islets but not in supernatants of isolated endocrine cells. The results indicate that IL-I/~ toxicity occurs via inducing in non-endocrine islet cells the synthesis and release of nitric oxide, which has been shown earlier to be highly toxic for islet cells, We have recently demonstrated that activated macrophages rapidly kill islet cells via arginine-dependent nitric oxide generation [11]. We now provide evidence that IL-1,8-mcdiated eytotoxicity involves nitric oxide formation by subpopulations of cells within the islet.

show abstract

Administration of Silica Prevents Diabetes in BB-Rats

Cited by 130 publications

References 7 publications

In CD4+ T-Cell-Induced Diabetes, Macrophages Are the Final Effector Cells that Mediate Islet β-Cell Killing

In CD4+ T-Cell-Induced Diabetes, Macrophages Are the Final Effector Cells that Mediate Islet β-Cell Killing

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

Cytotoxic action of IL‐1β against pancreatic islets is mediated via nitric oxide formation and is inhibited by N^G‐monomethyl‐l‐arginine

Contact Info

Product

Resources

About

Administration of Silica Prevents Diabetes in BB-Rats

Cited by 130 publications

References 7 publications

In CD4+ T-Cell-Induced Diabetes, Macrophages Are the Final Effector Cells that Mediate Islet β-Cell Killing

In CD4+ T-Cell-Induced Diabetes, Macrophages Are the Final Effector Cells that Mediate Islet β-Cell Killing

IL-1β and IFN-γ induce the expression of diverse chemokines and IL-15 in human and rat pancreatic islet cells, and in islets from pre-diabetic NOD mice

Cytotoxic action of IL‐1β against pancreatic islets is mediated via nitric oxide formation and is inhibited by NG‐monomethyl‐l‐arginine

Contact Info

Product

Resources

About

Cytotoxic action of IL‐1β against pancreatic islets is mediated via nitric oxide formation and is inhibited by N^G‐monomethyl‐l‐arginine