IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation
IL-10 deficiency increases superoxide and endothelial dysfunction during inflammation
复制标题
DOI：
10.1152/ajpheart.2000.279.4.h1555
复制
发表时间：
2000-10-01
影响因子：
4.8
通讯作者：
Faraci, FM
中科院分区：
文献类型：
--
作者：
Gunnett, CA;Heistad, DD;Faraci, FM
白细胞介素-10 (IL-10)，一种抗炎细胞因子，在血管中的作用知之甚少。我们使用IL-10缺陷小鼠（IL-10 -/-）来检验IL-10在脂多糖（LPS）处理后保护内皮功能的假设。在体外注射相对低剂量的LPS (10 μ g / ip) 6 h后，研究颈动脉的反应。IL-10 -/-小鼠对ACh （3 μ M）的最大松弛度LPS组为56 +/- 6%（平均+/- SE），载药组为84 +/- 4% （P< 0.05）。因此，注射LPS后IL-10 -/-小鼠颈动脉内皮依赖性松弛受损。相反，该剂量的LPS没有改变野生型（IL-10 +/+）小鼠血管中乙酰胆碱的松弛。IL-10 -/-和IL-10 +/+小鼠的动脉在载药或LPS注射后对硝普塞和罂粟碱的松弛相似。由于炎症与活性氧水平的增加有关，我们也验证了在缺乏IL-10的情况下，超氧化物通过LPS导致内皮功能受损的假设。用共聚焦显微镜和氢乙啶观察结果表明，与注射LPS后的IL-10 -/-小鼠相比，IL-10 +/+小鼠颈动脉超氧化物水平升高。用聚乙二醇悬浮型超氧化物歧化酶（50 U/ml）或黄嘌呤氧化酶抑制剂别嘌呤醇（1 mM）使注射LPS后IL-10 -/-小鼠的动脉舒张功能恢复正常。这些数据提供了直接证据，IL-10通过限制局部超氧化物的增加来保护急性炎症刺激后的内皮功能。该模型中超氧化物的来源可能是黄嘌呤氧化酶。
Little is known about the role of interleukin-10 (IL-10), an antiinflammatory cytokine, in blood vessels. We used IL-10-deficient mice (IL-10 -/-) to examine the hypothesis that IL-10 protects endothelial function after lipopolysaccharide (LPS) treatment. The responses of carotid arteries were studied in vitro 6 h after injection of a relatively low dose of LPS (10 mu g ip). In IL-10 -/- mice, the maximum relaxation to ACh (3 mu M) was 56 +/- 6% (means +/- SE) after LPS injection and 84 +/- 4% after vehicle injection (P< 0.05). Thus endothelium-dependent relaxation was impaired in carotid arteries from IL-10 -/- mice after LPS injection. In contrast, this dose of LPS did not alter relaxation to ACh in vessels from wild-type (IL-10 +/+) mice. Relaxation to nitroprusside and papaverine was similar in arteries from both IL-10 -/- and IL-10 +/+ mice after vehicle or LPS injection. Because inflammation is associated with increased levels of reactive oxygen species, we also tested the hypothesis that superoxide contributes to the impairment of endothelial function by LPS in the absence of IL-10. Results using confocal microscopy and hydroethidine indicated that levels of superoxide are elevated in carotid arteries from IL-10 -/- mice compared with IL-10 +/+ mice after LPS injection. The impaired relaxation of arteries from IL-10 -/- mice after LPS injection was restored to normal by polyethylene glycol-suspended superoxide dismutase (50 U/ml) or allopurinol (1 mM), an inhibitor of xanthine oxidase. These data provide direct evidence that IL-10 protects endothelial function after an acute inflammatory stimulus by limiting local increases in superoxide. The source of superoxide in this model may be xanthine oxidase.