Tumor Necrosis Factor-alpha Does Not Mediate Diabetes-Induced Vascular Inflammation in Mice Export

@article{citeulike:5793906, abstract = {Objective-- Vascular inflammation is a key feature of both micro- and macrovascular complications in diabetes. Several lines of evidence have implicated the cytokine tumor necrosis factor (TNF){alpha} as an important mediator of inflammation in diabetes. In the present study we evaluated the role of TNF{alpha} in streptozotocin (STZ)-induced diabetes on vascular inflammation in C57BL/6 wild-type and apoE-/- mice. Methods and Results-- Diabetes increased the expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries >150 {micro}m in diameter as well as the macrophage accumulation in aortic root atherosclerotic plaques in apoE-/- mice. A more pronounced vascular inflammatory response was observed in diabetic TNF{alpha}-deficient apoE-/- mice. These mice were also characterized by increased accumulation of IgG and IgM autoantibodies in atherosclerotic lesions. Diabetes also increased VCAM-1 expression and plaque formation in apoE-competent TNF{alpha}-/- mice, whereas no such effects were observed in C57BL/6 wild-type mice. Conclusions-- The present findings suggest that TNF{alpha} does not mediate diabetic-induced vascular inflammation in mice and reveal an unexpected protective role for TNF{alpha}. These effects are partly attributable to a direct antiinflammatory role of TNF{alpha}, but may also reflect a defective development of the immune system in these mice. Using C57BL/6 wild-type and apoE-/- mice deficient for TNF{alpha} we demonstrate that TNF{alpha} does not mediate vascular inflammation in response to streptozotocin-induced hyperglycemia. We also report evidence for a dysregulation of vascular inflammation in TNF{alpha}-/- mice revealing an unexpected protective role for this cytokine. 10.1161/ATVBAHA.109.193862}, author = {Nilsson-Ohman, Jenny and Fredrikson, Gunilla N. and Nilsson-Berglund, Lisa M. and Gustavsson, Carin and Bengtsson, Eva and Smith, Maj-Lis and Agardh, Carl-David and Agardh, Elisabet and Jovinge, Stefan and Gomez, Maria F. and Nilsson, Jan}, citeulike-article-id = {5793906}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/ATVBAHA.109.193862}, citeulike-linkout-1 = {http://atvb.ahajournals.org/cgi/content/abstract/29/10/1465}, day = {1}, doi = {10.1161/ATVBAHA.109.193862}, journal = {Arterioscler Thromb Vasc Biol}, keywords = {tnf}, month = {October}, number = {10}, pages = {1465--1470}, posted-at = {2009-09-17 03:40:25}, priority = {2}, title = {Tumor Necrosis Factor-{alpha} Does Not Mediate Diabetes-Induced Vascular Inflammation in Mice}, url = {http://dx.doi.org/10.1161/ATVBAHA.109.193862}, volume = {29}, year = {2009} }

TY - JOUR ID - citeulike:5793906 L3 - citeulike-article-id:5793906 N2 - Objective-- Vascular inflammation is a key feature of both micro- and macrovascular complications in diabetes. Several lines of evidence have implicated the cytokine tumor necrosis factor (TNF){alpha} as an important mediator of inflammation in diabetes. In the present study we evaluated the role of TNF{alpha} in streptozotocin (STZ)-induced diabetes on vascular inflammation in C57BL/6 wild-type and apoE-/- mice. Methods and Results-- Diabetes increased the expression of vascular cell adhesion molecule (VCAM)-1 in cerebral arteries >150 {micro}m in diameter as well as the macrophage accumulation in aortic root atherosclerotic plaques in apoE-/- mice. A more pronounced vascular inflammatory response was observed in diabetic TNF{alpha}-deficient apoE-/- mice. These mice were also characterized by increased accumulation of IgG and IgM autoantibodies in atherosclerotic lesions. Diabetes also increased VCAM-1 expression and plaque formation in apoE-competent TNF{alpha}-/- mice, whereas no such effects were observed in C57BL/6 wild-type mice. Conclusions-- The present findings suggest that TNF{alpha} does not mediate diabetic-induced vascular inflammation in mice and reveal an unexpected protective role for TNF{alpha}. These effects are partly attributable to a direct antiinflammatory role of TNF{alpha}, but may also reflect a defective development of the immune system in these mice. Using C57BL/6 wild-type and apoE-/- mice deficient for TNF{alpha} we demonstrate that TNF{alpha} does not mediate vascular inflammation in response to streptozotocin-induced hyperglycemia. We also report evidence for a dysregulation of vascular inflammation in TNF{alpha}-/- mice revealing an unexpected protective role for this cytokine. 10.1161/ATVBAHA.109.193862 IS - 10 JF - Arterioscler Thromb Vasc Biol EP - 1470 TI - Tumor Necrosis Factor-{alpha} Does Not Mediate Diabetes-Induced Vascular Inflammation in Mice VL - 29 SP - 1465 KW - tnf AU - Nilsson-Ohman, Jenny AU - Fredrikson, Gunilla AU - Nilsson-Berglund, Lisa AU - Gustavsson, Carin AU - Bengtsson, Eva AU - Smith, Maj-Lis AU - Agardh, Carl-David AU - Agardh, Elisabet AU - Jovinge, Stefan AU - Gomez, Maria AU - Nilsson, Jan PY - 2009/10/01/ UR - http://dx.doi.org/10.1161/ATVBAHA.109.193862 ER -