SPLUNC1 regulation in airway epithelial cells: role of Toll-like receptor 2 signaling.
SPLUNC1 regulation in airway epithelial cells: role of Toll-like receptor 2 signaling.
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DOI：
10.1186/1465-9921-11-155
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发表时间：
2010-11-05
影响因子：
5.8
通讯作者：
Martin RJ
中科院分区：
文献类型：
--
作者：
Chu HW;Gally F;Thaikoottathil J;Janssen-Heininger YM;Wu Q;Zhang G;Reisdorph N;Case S;Minor M;Smith S;Jiang D;Michels N;Simon G;Martin RJ
包括肺炎支原体（Mp）在内的呼吸道感染导致各种慢性肺部疾病。我们已经表明，小鼠短腭，肺，鼻上皮克隆1（SPLUNC 1）蛋白能够抑制MP的生长。此外，气道上皮细胞增加SPLUNC 1表达后，MP感染。然而，SPLUNC 1调控的潜在机制仍然未知。在目前的研究中，我们研究了Mp感染后SPLUNC 1的产生是否通过Toll样受体2（TLR 2）信号转导进行调节。利用气道上皮细胞培养物来揭示在细菌感染和TLR 2激动剂刺激后TLR 2信号传导（包括NF-κB）对SPLUNC 1产生的贡献。Mp和TLR 2激动剂Pam 3CSK 4增加野生型小鼠气管上皮细胞SPLUNC 1的表达，但不增加TLR 2-/- BALB/c小鼠气管上皮细胞SPLUNC 1的表达。在空气-液体界面培养下的正常人支气管上皮细胞中的TLR 2的RNA干扰（短发夹RNA）显著降低MP感染或Pam 3CSK 4处理的细胞中的SPLUNC 1水平。抑制和激活NF-κB通路分别减少和增加气道上皮细胞SPLUNC 1的产生。我们的数据首次表明，气道上皮细胞TLR 2信号转导在支原体诱导的SPLUNC 1产生中起关键作用，从而提高了我们对患有慢性肺部疾病伴细菌感染患者气道中SPLUNC 1异常表达的理解。
Respiratory infections including Mycoplasma pneumoniae (Mp) contribute to various chronic lung diseases. We have shown that mouse short palate, lung, and nasal epithelium clone 1 (SPLUNC1) protein was able to inhibit Mp growth. Further, airway epithelial cells increased SPLUNC1 expression upon Mp infection. However, the mechanisms underlying SPLUNC1 regulation remain unknown. In the current study, we investigated if SPLUNC1 production following Mp infection is regulated through Toll-like receptor 2 (TLR2) signaling. Airway epithelial cell cultures were utilized to reveal the contribution of TLR2 signaling including NF-κB to SPLUNC1 production upon bacterial infection and TLR2 agonist stimulation. Mp and TLR2 agonist Pam3CSK4 increased SPLUNC1 expression in tracheal epithelial cells from wild type, but not TLR2-/- BALB/c mice. RNA interference (short-hairpin RNA) of TLR2 in normal human bronchial epithelial cells under air-liquid interface cultures significantly reduced SPLUNC1 levels in Mp-infected or Pam3CSK4-treated cells. Inhibition and activation of NF-κB pathway decreased and increased SPLUNC1 production in airway epithelial cells, respectively. Our data for the first time suggest that airway epithelial TLR2 signaling is pivotal in mycoplasma-induced SPLUNC1 production, thus improving our understanding of the aberrant SPLUNC1 expression in airways of patients suffering from chronic lung diseases with bacterial infections.
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影响因子：
4.4
作者：
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DOI：
10.1164/rccm.200707-1096oc
发表时间：
2008-05-01
影响因子：
24.7
作者：
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通讯作者：
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