Interleukin-10 inhibits the in vivo and in vitro adverse effects of TNF-[alpha] on the endothelium of murine aorta

TNF-α 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-α-induced endothelial dysfunction in murine aorta. In in vitro experiments, aortic rings of C57BL/6 female mice we...

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Bibliographic Details
Published in:American journal of physiology. Heart and circulatory physiology 2010-10, Vol.299 (4), p.H1160
Main Authors: Zemse, Saiprasad M, Chiao, Chin Wei, Hilgers, Rob H P, Webb, R Clinton
Format: Article
Language:English
Subjects:
Cells
Coronary vessels
Cytokines
Gene expression
Nitric oxide
Rodents
Studies
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Summary:TNF-α 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-α-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 ...), TNF-α (4 nmol/l), or recombinant mouse IL-10 (300 ng/ml) or in the presence of both TNF-α and IL-10 for 22 h at 37...C. In in vivo experiments C57BL6/IL-10 knockout female mice were treated with saline or TNF-α (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 ...mol/l) during phenylephrine (10 ...mol/l)-induced contraction. As a result, overnight exposure of aortic rings to TNF-α resulted in significant blunted maximal relaxing responses (...) to ACh compared with untreated rings (22 ± 4 vs. 82 ± 3%, respectively). IL-10 knockout mice treated with TNF-α showed significant impairment in ACh responses (...) compared with C57BL/6 mice treated with TNF-α (51 ± 3 vs. 72 ± 3%, respectively). Western blot analysis showed that endothelial nitric oxide synthase (eNOS) expression was reduced by TNF-α 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-α by protecting eNOS expression. (ProQuest: ... denotes formulae/symbols omitted.)
ISSN:0363-6135
1522-1539