The effects of leptin on airway smooth muscle responses
The effects of leptin on airway smooth muscle responses
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DOI：
10.1165/rcmb.2007-0091oc
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发表时间：
2008-10-01
影响因子：
6.4
通讯作者：
Cox, P. Gerard
中科院分区：
文献类型：
--
作者：
Nair, Paranneswaran;Radford, Katherine;Cox, P. Gerard
肥胖与哮喘和呼吸道高反应性有关。瘦素调节肥胖症中观察到的一些促炎效应。本研究的目的是确定瘦素对气道平滑肌反应的影响。观察了瘦素(0.1-100 ng/ml)对9例非哮喘供者培养的人气道平滑肌细胞迁移(10 ng/ml)、增殖(BrDU掺入法)和细胞因子产生(BioPlex珠法)的影响。本文研究了瘦素对牛气管平滑肌环收缩反应的影响。用免疫印迹和聚合酶链式反应检测瘦素受体、STAT-3、细胞因子信号转导抑制因子-3(SoCS-3)和COX的活化。用酶免疫法测定培养上清液中前列腺素E(2)水平。人的呼吸道平滑肌细胞表达瘦素受体，当参与时，它会磷酸化STAT-3。瘦素可抑制PDGF诱导的人气道平滑肌迁移和增殖以及IL-13诱导的嗜酸性粒细胞趋化因子的产生。瘦素不能刺激细胞因子的合成，也不能引起收缩反应，也不能抑制异丙肾上腺素对卡巴胆碱引起的牛气管环收缩的松弛作用。对迁移和嗜酸性粒细胞趋化因子产生的抑制作用不是由于SOCS-3的激活，而是由于消炎痛减弱了PGE2的产生。总而言之，瘦素抑制了人的气道平滑肌的增殖、向PDGF的迁移和IL-13诱导的嗜酸性粒细胞趋化因子的产生。这在一定程度上是由瘦素诱导的平滑肌细胞分泌PGE2介导的。肥胖和哮喘之间的联系不太可能是由于瘦素对呼吸道平滑肌的直接影响。
Obesity is associated with asthma and airway hyperresponsiveness. Leptin modulates some of the proinflammatory effects observed in obesity. The objective of this study was to determine the effects of leptin on airway smooth muscle responses. The effect of leptin (0.1-100 ng/ml) on migration (toward platelet-derived growth factor [PDGF], 10 ng/ml, across collagen-coated membrane in Transwell culture plates), proliferation (by BrDU incorporation), and cytokine production (by Bioplex bead assay) of cultured human airway smooth muscle cells from nine nonasthmatic donors was assessed. Effects of leptin on the contractile responses were studied in bovine tracheal smooth muscle rings. Leptin receptor expression and activation of STAT-3, Src kinase, Suppressor of Cytokine Signaling-3 (SOCS-3), and COX were evaluated by Western blotting and PCR. PGE(2) levels in supernatant were assessed by enzyme immunoassay. Human airway smooth muscle cells express leptin receptor, which, when engaged, phosphorylated STAT-3. Leptin inhibited PDGF-induced human airway smooth muscle migration and proliferation and IL-13-induced eotaxin production. Leptin did not stimulate cytokine synthesis and did not evoke contractile responses or inhibit isoproterenol-induced relaxation of carbachol-induced contraction of bovine tracheal rings. The inhibitory effects on migration and eotaxin production are not due to activation of SOCS-3 but are partly due to increased production of PGE2 because they were attenuated by indomethacin. In conclusion, leptin inhibited human airway smooth muscle proliferation, migration toward PDGF, and IL-13-induced eotaxin production. This is partly mediated by PGE2 secretion from smooth muscle cells induced by leptin. The association between obesity and asthma is unlikely to be due to a direct effect of leptin on airway smooth muscle.