Differential Expression of ICAM-1 and LFA-1 versus L-selectin and VCAM-1 in Autoimmune Insulitis of NOD Mice and Association with both Th1- and Th2-type Infiltrates

Martin, Stéphan; Hibino, Takeshi; Faust, Antje; Kleemann, R.; Kolb, Hubert

doi:10.1006/jaut.1996.0083

Cited by 22 publications

(18 citation statements)

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“…In vitro islet studies revealed that ICAM-1 expression can be induced by different cytokines [4]. However, in vivo, we and others observed ICAM-1 expression in infiltrated islets of NOD mice only on infiltrating immune cells, but not on -cells [5,6].…”

Section: Introductionmentioning

confidence: 69%

“…Pancreatic tissue was snap frozen in liquid nitrogen and analysed as described previously [5]. Semiquantitative histological analysis was performed on haematoxylin-eosin stained sections by two independent investigators.…”

Section: Histologymentioning

confidence: 99%

“…Histological scores give the mean infiltration grade of islets analysed. Staining for ICAM-1 was performed with the monoclonal antibody YN1/1.7.4 as described previously [5].…”

Section: Histologymentioning

confidence: 99%

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Dominant Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Autoimmune Diabetes in Non-obese Diabetic Mice

Martin

Engel

Vinke

et al. 2001

Journal of Autoimmunity

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Section: Introductionmentioning

confidence: 69%

Section: Histologymentioning

confidence: 99%

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Dominant Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Autoimmune Diabetes in Non-obese Diabetic Mice

Martin

Engel

Vinke

et al. 2001

Journal of Autoimmunity

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“…Histological examination of pancreatic islets was done as described previously [17]. A total of 60 islets per group were analysed, at least 10 islets per animal.…”

Section: Subjects Materials and Methodsmentioning

confidence: 99%

Soluble forms of intercellular adhesion molecule-1 inhibit insulitis and onset of autoimmune diabetes

et al. 1998

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“…activation in leukocytes, and to decrease adhesion molecule (ICAM-1) expression on monocytes and in stimulated endothelial cells (Niwa et al, 1996;Romano et al, 2000;Takeuchi et al, 2000;Yoshida et al, 2001). Of these, ICAM-1 and LFA-1 have been shown to be expressed in pancreatic islets with a peri-insular infiltration of mononuclear cells as well as in islets with an intraislet infiltration in NOD mice (Martin et al, 1996). Based on these findings, we suggest that the protective effect of simvastatin observed presently in the MLDS and ROD model of type 1 diabetes is probably related to the anti-inflammatory actions described above.…”

Section: Simvastatin Protection Against Murine Type 1 Diabetes 183mentioning

confidence: 99%

Simvastatin Protects against Multiple Low-Dose Streptozotocin-Induced Type 1 Diabetes in CD-1 Mice and Recurrence of Disease in Nonobese Diabetic Mice

Rydgren¹,

Vaarala²,

Sandler³

2007

J Pharmacol Exp Ther

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Statins are drugs well known for their cholesterol-lowering properties. Lately, statins have been shown to possess antiinflammatory properties that might be attributed to inhibition of leukocyte adhesion and migration to sites of inflammation. Therefore, we have explored the effects of administration of simvastatin (30 mg/kg body weight given i.p. once a day, from days 4 -14) on the development of diabetes induced by multiple low-dose streptozotocin (MLDS) in CD-1 mice, a type 1 diabetes model. We found that treatment with simvastatin could delay and in certain mice fully protect against MLDS-induced diabetes. The protective effect could last up to 3 weeks after simvastatin treatment was ended. Morphological examinations of the pancreas suggest that simvastatin might reduce the islet inflammation. Based on experiments in vitro, using isolated pancreatic islets, we conclude that the protective effect of simvastatin is not mediated by a direct effect on streptozotocin action but rather the result of an immunomodulatory effect. This was reinforced by the finding that simvastatin treatment also prolonged islet function in the recurrence of disease model in diabetic nonobese diabetic mice.Simvastatin (for chemical structure, see Weitz-Schmidt, 2002) belongs to the statin family, a class of drugs that competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, the rate-limiting step of the cholesterol synthesis pathway. Statins are frequently prescribed to prevent coronary heart disease and have been shown to exert this action even without a significant drop in blood cholesterol levels, suggesting anti-inflammatory properties independent of its cholesterol-lowering effects (Downs et al., 1998;Ridker et al., 1998;Weitz-Schmidt, 2002).Mevalonate is a precursor not only for cholesterol but also for isoprenoids, such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate. These are necessary for the posttranslational lipid modification of a variety of proteins belonging to the small GTP binding proteins, e.g., Ras, Rho, and Rab (Weitz-Schmidt, 2002). Statins might therefore prevent the membrane localization and function of these proteins by inhibiting HMG-CoA reductase. There is strong evidence that these effects of statins, at least in part, are the basis for its anti-inflammatory properties. For example, Liu et al. (1999) have shown that inhibition of integrin activation by statins correlates with the reduced geranylgeranylation of Rho, and Takeuchi et al. (2000) have shown that statins prevent intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells by blocking Rho activation.Some statins, including simvastatin, have also been shown to bind to an allosteric site of the integrin leukocyte functionassociated antigen-1 (LFA-1), locking LFA-1 in its inactive form, thereby preventing LFA-1-mediated adhesion and costimulation of lymphocytes (Weitz-Schmidt et al., 2001). In addition, simvastatin has recently been...

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Differential Expression of ICAM-1 and LFA-1 versus L-selectin and VCAM-1 in Autoimmune Insulitis of NOD Mice and Association with both Th1- and Th2-type Infiltrates

Cited by 22 publications

References 0 publications

Dominant Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Autoimmune Diabetes in Non-obese Diabetic Mice

Dominant Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Autoimmune Diabetes in Non-obese Diabetic Mice

Soluble forms of intercellular adhesion molecule-1 inhibit insulitis and onset of autoimmune diabetes

Simvastatin Protects against Multiple Low-Dose Streptozotocin-Induced Type 1 Diabetes in CD-1 Mice and Recurrence of Disease in Nonobese Diabetic Mice

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