Vascular interleukin-10 protects against LPS-induced vasomotor dysfunction
Vascular interleukin-10 protects against LPS-induced vasomotor dysfunction
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DOI：
10.1152/ajpheart.01234.2004
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发表时间：
2005-08-01
影响因子：
4.8
通讯作者：
Heistad, DD
中科院分区：
文献类型：
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作者：
Gunnett, CA;Lund, DD;Heistad, DD
我们测试了以下假设：1）腺病毒基因转移后，全身性IL-10保护动脉免受LPS引起的舒张受损; 2）动脉壁内IL-10的局部表达保护LPS后的血管功能障碍; 3）IL-10保护LPS后由诱导型NO合酶（iNOS）介导的血管功能障碍。在IL-10缺陷型（IL-10 -/-）和野生型（WT，IL-10 +/+）小鼠中，LPS在体内损害了动脉对乙酰胆碱的舒张，并且IL-10的基因转移改善了对乙酰胆碱的反应。LPS后动脉中的超氧化物水平升高，IL-10的基因转移阻止了超氧化物水平的增加。在体外与低浓度LPS孵育以消除来自非血管来源的LPS和IL-10的全身效应的动脉中，对乙酰胆碱的反应在IL-10缺陷小鼠中受损，并且通过IL-10的体外基因转移在很大程度上防止了损伤。在体外WT小鼠的动脉中，低浓度的LPS不会损害对乙酰胆碱的反应。因此，血管壁内的IL-10保护免受LPS诱导的功能障碍。在IL-10缺陷的小鼠中，氨基胍，抑制iNOS，保护LPS后的血管功能障碍。在iNOS缺陷小鼠的动脉中，LPS不损害对乙酰胆碱的反应。这些发现表明，IL-10的全身和局部作用都提供了重要的动脉保护作用，以对抗炎症刺激，并且IL-10降低了LPS后iNOS介导的血管舒张损伤。
We tested the hypotheses that 1) systemic IL-10, after adenoviral gene transfer, protects arteries from impaired relaxation produced by LPS; 2) local expression of IL-10 within the arterial wall protects against vasomotor dysfunction after LPS; and 3) IL-10 protects against vascular dysfunction mediated by inducible NO synthase ( iNOS) after LPS. In IL-10-deficient (IL-10 -/-) and wild-type (WT, IL-10 +/+) mice, LPS in vivo impaired relaxation of arteries to acetylcholine and gene transfer of IL-10 improved responses to acetylcholine. Superoxide levels were elevated in arteries after LPS, and increased levels of superoxide were prevented by gene transfer of IL-10. In arteries incubated with a low concentration of LPS in vitro to eliminate systemic effects of LPS and IL-10 from nonvascular sources, responses to acetylcholine were impaired in IL-10-deficient mice and impairment was largely prevented by gene transfer in vitro of IL-10. In arteries from WT mice in vitro, the low concentration of LPS did not impair responses to acetylcholine. Thus IL-10 within the vessel wall protects against LPS-induced dysfunction. In IL-10-deficient mice, aminoguanidine, which inhibits iNOS, protected against vasomotor dysfunction after LPS. In arteries from iNOS-deficient mice, LPS did not impair responses to acetylcholine. These findings suggest that both systemic and local effects of IL-10 provide important protection of arteries against an inflammatory stimulus and that IL-10 decreases iNOS-mediated impairment of vasorelaxation after LPS.