Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice.
Impact of interleukin-6 on hypoxia-induced pulmonary hypertension and lung inflammation in mice.
复制标题
白介素6对小鼠缺氧诱导的肺动脉高压和肺部炎症的影响。
DOI：
10.1186/1465-9921-10-6
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发表时间：
2009-01-27
影响因子：
5.8
通讯作者：
Eddahibi S
中科院分区：
文献类型：
--
作者：
Savale L;Tu L;Rideau D;Izziki M;Maitre B;Adnot S;Eddahibi S
炎症可能导致各种形式的肺动脉高压（PH）的发病机制。最近在特发性PH或PH与基础疾病相关的患者中的研究表明白细胞介素-6（IL-6）的作用。为了确定内源性IL-6是否有助于介导缺氧PH和肺部炎症，我们研究了暴露于缺氧2周的IL-6缺陷型（IL-6-/-）和野生型（IL-6+/+）小鼠。缺氧2周后，与野生型对照组相比，IL-6-/-小鼠的右心室收缩压、右心室肥大以及肌性肺血管的数量和中膜厚度均降低，尽管IL-6+/+和IL-6-/-小鼠对急性缺氧的压力反应相似。缺氧暴露的IL-6+/+小鼠在第一周内导致IL-6 mRNA和蛋白水平显著增加，肺血管壁中IL-6免疫染色阳性。缺氧1周和2周后，肺组织IL-6受体和IL-6信号转导分子gp 130 mRNA水平均升高.体外培养的人肺动脉平滑肌细胞（PA-SMCs）和微血管内皮细胞的研究表明，PA-SMCs的显著合成IL-6，进一步刺激缺氧。IL-6也显著刺激PA-SMC迁移而不影响增殖。通过肺蛋白水平和特异性巨噬细胞标记物F4/80的免疫染色评估，与缺氧野生型小鼠相比，缺氧IL-6-/-小鼠在肺中显示较少的炎性细胞募集，在粘附分子或细胞因子的肺表达中没有差异。这些数据表明，IL-6可能积极参与缺氧诱导的小鼠肺部炎症和肺血管重塑。
Inflammation may contribute to the pathogenesis of various forms of pulmonary hypertension (PH). Recent studies in patients with idiopathic PH or PH associated with underlying diseases suggest a role for interleukin-6 (IL-6). To determine whether endogenous IL-6 contributes to mediate hypoxic PH and lung inflammation, we studied IL-6-deficient (IL-6-/-) and wild-type (IL-6+/+) mice exposed to hypoxia for 2 weeks. Right ventricular systolic pressure, right ventricle hypertrophy, and the number and media thickness of muscular pulmonary vessels were decreased in IL-6-/- mice compared to wild-type controls after 2 weeks' hypoxia, although the pressure response to acute hypoxia was similar in IL-6+/+ and IL-6-/- mice. Hypoxia exposure of IL-6+/+ mice led to marked increases in IL-6 mRNA and protein levels within the first week, with positive IL-6 immunostaining in the pulmonary vessel walls. Lung IL-6 receptor and gp 130 (the IL-6 signal transducer) mRNA levels increased after 1 and 2 weeks' hypoxia. In vitro studies of cultured human pulmonary-artery smooth-muscle-cells (PA-SMCs) and microvascular endothelial cells revealed prominent synthesis of IL-6 by PA-SMCs, with further stimulation by hypoxia. IL-6 also markedly stimulated PA-SMC migration without affecting proliferation. Hypoxic IL-6-/- mice showed less inflammatory cell recruitment in the lungs, compared to hypoxic wild-type mice, as assessed by lung protein levels and immunostaining for the specific macrophage marker F4/80, with no difference in lung expression of adhesion molecules or cytokines. These data suggest that IL-6 may be actively involved in hypoxia-induced lung inflammation and pulmonary vascular remodeling in mice.
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影响因子：
32.4
作者：
Romano, M;Sironi, M;Mantovani, A
通讯作者：
Mantovani, A
影响因子：
39.2
作者：
Maggiorini, Marco;Brunner-La Rocca, Hans-Peter;Mairbaeurl, Heimo
通讯作者：
Mairbaeurl, Heimo
DOI：
10.1073/pnas.161272598
发表时间：
2001-07-17
影响因子：
11.1
作者：
Minamino, T;Christou, H;Kourembanas, S
通讯作者：
Kourembanas, S
DOI：
10.1164/rccm.2012112
发表时间：
2002-02-15
影响因子：
24.7
作者：
Dorfmüller, P;Zarka, V;Humbert, M
通讯作者：
Humbert, M
影响因子：
--
作者：
Marasini, Bianca;Cossutta, Roberta;Selmi, Carlo;Pozzi, Maria Rosa;Gardinali, Marco;Massarotti, Marco;Erario, Maddalena;Battaglioli, Lodovica;Biondi, Maria Luisa
通讯作者：
Biondi, Maria Luisa