Gunnett Carol A, Lund Donald D, Faraci Frank M, Heistad Donald D
Department of Internal Medicine, Univ. of Iowa Carver College of Medicine, Iowa City, IA 52242-6778, USA.
Am J Physiol Heart Circ Physiol. 2005 Aug;289(2):H624-30. doi: 10.1152/ajpheart.01234.2004.
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.
1）腺病毒基因转移后，全身性白细胞介素-10（IL-10）可保护动脉免受脂多糖（LPS）所致的舒张功能受损；2）动脉壁内IL-10的局部表达可预防LPS后的血管舒缩功能障碍；3）IL-10可预防LPS后由诱导型一氧化氮合酶（iNOS）介导的血管功能障碍。在IL-10基因缺陷（IL-10-/-）和野生型（WT，IL-10+/+）小鼠中，体内LPS损害了动脉对乙酰胆碱的舒张反应，而IL-10基因转移改善了对乙酰胆碱的反应。LPS后动脉中超氧化物水平升高，而IL-10基因转移可防止超氧化物水平升高。在体外与低浓度LPS孵育的动脉中，以消除LPS和IL-10来自非血管来源的全身效应，IL-10基因缺陷小鼠对乙酰胆碱的反应受损，而体外IL-10基因转移在很大程度上预防了这种损害。在体外WT小鼠的动脉中，低浓度LPS并未损害对乙酰胆碱的反应。因此，血管壁内的IL-10可预防LPS诱导的功能障碍。在IL-10基因缺陷小鼠中，抑制iNOS的氨基胍可预防LPS后的血管舒缩功能障碍。在iNOS基因缺陷小鼠的动脉中，LPS并未损害对乙酰胆碱的反应。这些发现表明，IL-10的全身和局部作用均为动脉提供了针对炎症刺激的重要保护，且IL-10可减轻LPS后iNOS介导的血管舒张功能损害。
