| First Author | Zemse SM | Year | 2010 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 299 |
| Issue | 4 | Pages | H1160-7 |
| PubMed ID | 20639218 | Mgi Jnum | J:162772 |
| Mgi Id | MGI:4819879 | Doi | 10.1152/ajpheart.00763.2009 |
| Citation | Zemse SM, et al. (2010) Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-alpha on the endothelium of murine aorta. Am J Physiol Heart Circ Physiol 299(4):H1160-7 |
| abstractText | TNF-alpha is a proinflammatory cytokine and is an important mediator of maternal endothelial dysfunction leading to preeclampsia. In this study, we tested whether IL-10 protects against TNF-alpha-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice were incubated in Dulbecco's modified Eagle's medium in the presence of either vehicle (distilled H(2)O), TNF-alpha (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-alpha and IL-10 for 22 h at 37 degrees C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-alpha (220 ng.kg(-1).day(-1)) for 14 days. Aortic rings were isolated from in vitro and in vivo experiments and mounted in a wire myograph (Danish Myotech) and stretched to a tension of 5 mN. Endothelium-dependent relaxation was assessed by constructing cumulative concentration-response curves to acetylcholine (ACh, 0.001-10 mumol/l) during phenylephrine (10 mumol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-alpha resulted in significant blunted maximal relaxing responses (E(max)) to ACh compared with untreated rings (22 +/- 4 vs. 82 +/- 3%, respectively). IL-10 knockout mice treated with TNF-alpha showed significant impairment in ACh responses (E(max)) compared with C57BL/6 mice treated with TNF-alpha (51 +/- 3 vs. 72 +/- 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-alpha in in vitro and in vivo experiments, whereas IL-10 restored the eNOS expression. In conclusion, the anti-inflammatory cytokine IL-10 prevents impairment in endothelium-dependent vasorelaxation caused by TNF-alpha by protecting eNOS expression. |
