Induction of regulated upon activation, normal T cells expressed and secreted (RANTES) and transforming growth factor-β1 in airway epithelial cells by Mycoplasma pneumoniae
Induction of regulated upon activation, normal T cells expressed and secreted (RANTES) and transforming growth factor-β1 in airway epithelial cells by Mycoplasma pneumoniae
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DOI：
10.1165/rcmb.2002-0291oc
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发表时间：
2003-09-01
影响因子：
6.4
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
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作者：
Dakhama, A;Kraft, M;Gelfand, EW
肺炎支原体感染会加剧儿童哮喘，并可能在慢性哮喘的发病机制中发挥作用。由于气道上皮是肺炎支原体感染的优先部位，也是调节活化、正常 T 细胞表达和分泌 (RANTES) 和转化生长因子 (TGF)-β1 趋化因子的主要来源，因此我们推测这种微生物可能通过与气道上皮细胞直接相互作用诱导这些介质而导致疾病。我们研究了肺炎支原体对正常人支气管上皮 (NHBE) 细胞和小气道上皮 (SAEC) 细胞原代培养物中 RANTES 和 TGF-β1 产生的影响。这两种细胞类型在体外都允许肺炎支原体感染，但它们的反应不同。 TGF-β1 在 NHBE 培养物中的诱导水平高于 SAEC 培养物，而 RANTES 在 SAEC 培养物中诱导，但在 NHBE 培养物中不诱导。红霉素和地塞米松可减弱这些作用。体外粘附测定进一步表明，红霉素的作用是通过其抗菌作用介导的，导致病原体粘附减少，而地塞米松的作用似乎不是通过抑制粘附来实现的。这些结果表明，肺炎支原体感染可能通过诱导大气道中的TGF-β1和小气道中的趋化因子RANTES，从而在气道的不同水平上促进慢性哮喘的发病机制。
Mycoplasma pneumoniae infection exacerbates asthma in children and may play a role in the pathogenesis of chronic asthma. Because the airway epithelium is a preferential site for M. pneumoniae infection and a major source of the chemokine regulated on activation, normal T cells expressed and secreted (RANTES) and transforming growth factor (TGF)-beta1, we postulated that this microorganism may contribute to the disease by inducing these mediators through direct interaction with airway epithelial cells. We investigated the effects of M. pneumoniae on RANTES and TGF-beta1 production in primary cultures of normal human bronchial epithelial (NHBE) cells and small airway epithelial (SAEC) cells. Both cell types were permissive to M. pneumoniae infection in vitro, but their responses were different. TGF-beta1 was induced at higher levels in NHBE than in SAEC cultures, whereas RANTES was induced in SAEC cultures but not in NHBE cultures. These effects were attenuated by erythromycin and dexamethasone. In vitro adherence assays further indicated that the effects of erythromycin were mediated through its antimicrobial action, resulting in diminished adherence of the pathogen, whereas the effects of dexamethasone did not appear to be by inhibition of adherence. These results suggest that M. pneumoniae infection may contribute to the pathogenesis of chronic asthma at different levels of the airways, by inducing TGF-beta1 in large airways and the chemokine RANTES in small airways.