Upregulation of IL-17A/F from human lung tissue explants with cigarette smoke exposure: implications for COPD.
Upregulation of IL-17A/F from human lung tissue explants with cigarette smoke exposure: implications for COPD.
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DOI：
10.1186/s12931-014-0145-7
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发表时间：
2014-11-27
影响因子：
5.8
通讯作者：
Eidelman DH
中科院分区：
文献类型：
--
作者：
Chang Y;Al-Alwan L;Alshakfa S;Audusseau S;Mogas AK;Chouiali F;Nair P;Baglole CJ;Hamid Q;Eidelman DH
慢性阻塞性肺病（COPD）是一种炎症性疾病，其特点是对类固醇相对抵抗。 IL-17 超家族介导适应性免疫系统和先天免疫系统之间的交互作用，与类固醇反应减弱有关。越来越多的证据支持 COPD 受试者肺部 IL-17 表达升高。然而，免疫系统（全身）细胞和/或局部肺细胞是否导致 IL-17 升高仍不清楚。为了解决这个问题，我们利用暴露于香烟烟雾的人肺实质组织外植体培养系统来研究 IL-17 的表达及其相关机制。从 10 名非慢性阻塞性肺病患者和 8 名慢性阻塞性肺病患者身上取出肺实质组织，进行切片并用不同浓度的香烟烟雾提取物 (CSE) 培养 3 或 6 小时。通过培养物上清液中的 LDH（乳酸脱氢酶）评估组织活力。进行蛋白质印迹和实时PCR来评估IL-17A/F表达。为了研究其机制，将 MAPK p38、ERK1/2、NF-κB 和 PI3K 通路的药理学抑制剂添加到培养基中。与对照介质相比，接触香烟烟雾 3 小时或 6 小时后未观察到组织损伤。在蛋白质水平上，非 COPD 受试者组织中 IL-17A（2.4±0.6 倍）和 IL-17 F（3.7±0.7 倍）的表达在 3 小时时显着增加 CSE 的 5%。对于 COPD 受试者，IL-17A/F 表达仅在 10% CSE 的 6 小时内显着增加（IL-17A：4.2±0.8 倍；IL-17F：3.3±0.8 倍）。 IL-17A/F 表达的增加也在 mRNA 水平上受到调节。 NF-κB 和 PI3K 通路抑制剂显着抑制 CSE 诱导的非 COPD 受试者肺组织中 IL-17A/F 的表达。我们发现有证据表明，非慢性阻塞性肺病和慢性阻塞性肺病受试者的外植体中，IL-17A 和 IL-17 F 的表达都会因接触香烟烟雾而增加，这支持局部肺细胞有助于 IL-17 的产生。 IL-17A/F 表达升高依赖于 NF-κB 和 PI3K 通路。这些观察结果进一步证明 Th17 细胞因子在 COPD 中发挥着重要作用。
Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked by relative resistance to steroids. The IL-17 superfamily, which mediates cross-talk between the adaptive and innate immune systems, has been associated with diminished responses to steroids. Increasing evidence supports elevated IL-17 expression in the lung of COPD subjects. However, whether cells of the immune system (systemic) and/or local lung cells are contributing to the elevated IL-17 remains unclear. To address this issue, we utilized a human parenchymal lung tissue explant culture system with cigarette smoke exposure to investigate the expression of IL-17 and the mechanisms involved. Parenchymal lung tissue removed from 10 non-COPD and 8 COPD patients was sectioned and cultured with different concentrations of cigarette smoke extract (CSE) for 3 or 6 hours. Tissue viability was evaluated by LDH (lactate dehydrogenase) in culture supernatants. Western blot and real-time PCR were performed to evaluate IL-17A/F expression. To investigate the mechanisms, pharmacological inhibitors for MAPK p38, ERK1/2, NF-κB and PI3K pathways were added into the culture media. No tissue damage was observed after the cigarette smoke exposure for 3 h or 6 h compared with the control media. At the protein level, the expression of both IL-17A (2.4 ± 0.6 fold) and IL-17 F (3.7 ± 0.7 fold) in the tissue from non-COPD subjects was significantly increased by 5% of CSE at 3 h. For COPD subjects, IL-17A/F expression were significantly increased only at 6 h with 10% of CSE (IL-17A: 4.2 ± 0.8 fold; IL-17 F: 3.3 ± 0.8 fold). The increased expression of IL-17A/F is also regulated at the mRNA level. The inhibitors for NF-κB and PI3K pathways significantly inhibited CSE-induced IL-17A/F expression from lung tissue of non-COPD subjects. We found the evidence that the expression of both IL-17A and IL-17 F is increased by the cigarette smoke exposure in explants from both non-COPD and COPD subjects, supporting that local lung cells contribute IL-17 production. The elevated IL-17A/F expression is dependent on NF-κB and PI3K pathways. These observations add to the growing evidence which suggests that Th17 cytokines play a significant role in COPD.
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影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
7.3
作者：
Birkenkamp, KU;Tuyt, LML;Vellenga, E
通讯作者：
Vellenga, E
影响因子：
20.3
作者：
Noubade, Rajkumar;Krementsov, Dimitry N.;Teuscher, Cory
通讯作者：
Teuscher, Cory
影响因子：
9.6
作者：
Cosio, MG;Majo, J;Cosio, MG
通讯作者：
Cosio, MG
影响因子：
5.8
作者：
Morissette MC;Jobse BN;Thayaparan D;Nikota JK;Shen P;Labiris NR;Kolbeck R;Nair P;Humbles AA;Stämpfli MR
通讯作者：
Stämpfli MR