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Sphingosine-1 phosphate prevents monocyte/endothelial interactions in type 1 diabetic NOD mice through activation of the S1P1 receptor.
Circ Res. 2006 Sep 29; 99(7):731-9.CircR

Abstract

Monocyte recruitment and adhesion to vascular endothelium are key early events in atherosclerosis. We examined the role of sphingosine-1-phosphate (S1P) on modulating monocyte/endothelial interactions in the NOD/LtJ (NOD) mouse model of type 1 diabetes. Aortas from nondiabetic and diabetic NOD mice were incubated in the absence or presence of 100 nmol/L S1P. Fluorescently labeled monocytes were incubated with the aortas. Aortas from NOD diabetic mice bound 7-fold more monocytes than nondiabetic littermates (10+/-1 monocytes bound/field for nondiabetic mice vs 74+/-12 monocytes bound/field for diabetic mice, P<0.0001). Incubation of diabetic aortas with 100 nmol/L S1P reduced monocyte adhesion to endothelium by 90%. We found expression of S1P1, S1P2, and S1P3 receptors on NOD aortic endothelial cells. The S1P1 receptor-specific agonist SEW2871 inhibited monocyte adhesion to diabetic aortas. Studies in diabetic S1P3-deficient mice revealed that the S1P3 receptor did not play a pivotal role in this process. S1P reduced endothelial VCAM-1 induction in type 1 diabetic NOD mice, most likely through inhibition of nuclear factor kappaB translocation to the nucleus. Thus, S1P activation of the S1P1 receptor functions in an antiinflammatory manner in type 1 diabetic vascular endothelium to prevent monocyte/endothelial interactions. S1P may play an important role in the prevention of vascular complications of type 1 diabetes.

Authors+Show Affiliations

Cardiovascular Research Center, University of Virginia, 415 Lane Rd, Charlottesville, VA 22908, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16960101

Citation

Whetzel, Angela M., et al. "Sphingosine-1 Phosphate Prevents Monocyte/endothelial Interactions in Type 1 Diabetic NOD Mice Through Activation of the S1P1 Receptor." Circulation Research, vol. 99, no. 7, 2006, pp. 731-9.
Whetzel AM, Bolick DT, Srinivasan S, et al. Sphingosine-1 phosphate prevents monocyte/endothelial interactions in type 1 diabetic NOD mice through activation of the S1P1 receptor. Circ Res. 2006;99(7):731-9.
Whetzel, A. M., Bolick, D. T., Srinivasan, S., Macdonald, T. L., Morris, M. A., Ley, K., & Hedrick, C. C. (2006). Sphingosine-1 phosphate prevents monocyte/endothelial interactions in type 1 diabetic NOD mice through activation of the S1P1 receptor. Circulation Research, 99(7), 731-9.
Whetzel AM, et al. Sphingosine-1 Phosphate Prevents Monocyte/endothelial Interactions in Type 1 Diabetic NOD Mice Through Activation of the S1P1 Receptor. Circ Res. 2006 Sep 29;99(7):731-9. PubMed PMID: 16960101.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosine-1 phosphate prevents monocyte/endothelial interactions in type 1 diabetic NOD mice through activation of the S1P1 receptor. AU - Whetzel,Angela M, AU - Bolick,David T, AU - Srinivasan,Suseela, AU - Macdonald,Timothy L, AU - Morris,Margaret A, AU - Ley,Klaus, AU - Hedrick,Catherine C, Y1 - 2006/09/07/ PY - 2006/9/9/pubmed PY - 2006/10/19/medline PY - 2006/9/9/entrez SP - 731 EP - 9 JF - Circulation research JO - Circ Res VL - 99 IS - 7 N2 - Monocyte recruitment and adhesion to vascular endothelium are key early events in atherosclerosis. We examined the role of sphingosine-1-phosphate (S1P) on modulating monocyte/endothelial interactions in the NOD/LtJ (NOD) mouse model of type 1 diabetes. Aortas from nondiabetic and diabetic NOD mice were incubated in the absence or presence of 100 nmol/L S1P. Fluorescently labeled monocytes were incubated with the aortas. Aortas from NOD diabetic mice bound 7-fold more monocytes than nondiabetic littermates (10+/-1 monocytes bound/field for nondiabetic mice vs 74+/-12 monocytes bound/field for diabetic mice, P<0.0001). Incubation of diabetic aortas with 100 nmol/L S1P reduced monocyte adhesion to endothelium by 90%. We found expression of S1P1, S1P2, and S1P3 receptors on NOD aortic endothelial cells. The S1P1 receptor-specific agonist SEW2871 inhibited monocyte adhesion to diabetic aortas. Studies in diabetic S1P3-deficient mice revealed that the S1P3 receptor did not play a pivotal role in this process. S1P reduced endothelial VCAM-1 induction in type 1 diabetic NOD mice, most likely through inhibition of nuclear factor kappaB translocation to the nucleus. Thus, S1P activation of the S1P1 receptor functions in an antiinflammatory manner in type 1 diabetic vascular endothelium to prevent monocyte/endothelial interactions. S1P may play an important role in the prevention of vascular complications of type 1 diabetes. SN - 1524-4571 UR - https://www.unboundmedicine.com/medline/citation/16960101/Sphingosine_1_phosphate_prevents_monocyte/endothelial_interactions_in_type_1_diabetic_NOD_mice_through_activation_of_the_S1P1_receptor_ DB - PRIME DP - Unbound Medicine ER -