IL-4和IFN-γ对COPD患者肺成纤维细胞HIF-1α和TGF-β1表达的影响

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摘要目的探讨白细胞介素4（IL-4）和γ干扰素（IFN-γ）在慢性阻塞性肺疾病（COPD）患者气道重塑中的协同调控作用。方法 2017年12月～2018年8月由中南大学湘雅医学院海口附属医院胸外科收集肺组织，其中肺癌进行手术切除标本的正常肺组织（16例）和肺癌合并COPD（12例）的肺组织标本。分别从正常肺组织和合并COPD患者肺组织中分离鉴定肺成纤维细胞，利用qRT-PCR、Western blot方法检测缺氧诱导因子1α（HIF-1α）和转化生长因子β1（TGF-β1）的表达水平；用IL-4和IFN-γ分别刺激肺成纤维细胞，随后检测HIF-1α和TGF-β1的表达水平，评价IL-4和IFN-γ对肺成纤维细胞HIF-1α/TGF-β1的影响。结果与正常肺成纤维细胞比较，COPD患者肺成纤维细胞中HIF-1α、TGF-β1的mRNA水平呈显著升高（P ＜ 0.01）；IL-4可引起肺成纤维细胞HIF-1α和TGF-β1表达升高（P ＜ 0.05），且HIF-1α和TGF-β1的表达与IL-4作用时间呈正相关（R2 = 0.8736，P = 0.0018；R2 = 0.8637，P = 0.0223）；IFN-γ可抑制肺成纤维细胞HIF-1α和TGF-β1的表达（P ＜ 0.05），且HIF-1α和TGF-β1的表达与IFN-γ作用时间呈负相关（R2 = 0.8410，P = 0.0283；R2 = 0.8142，P = 0.0361）。结论 IL-4可促进COPD患者肺成纤维细胞HIF-1α和TGF-β1的表达，且HIF-1α和TGF-β1的表达与IL-4作用时间呈正相关；相反，IFN-γ可抑制COPD患者肺成纤维细胞HIF-1α和TGF-β1的表达，且HIF-1α和TGF-β1的表达与IFN-γ作用时间呈负相关。

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	曾慈梅1 欧宗兴1 黄邓高2 沈彬1 王蕾1 马西淼3 曹卉2

关键词 ：白细胞介素-4, &gamma, 干扰素, 缺氧诱导因子1&alpha, 转化生长因子, 慢性阻塞性肺疾病气道重塑

Abstract：Objective To investigate the synergistic regulation of interleukin 4 (IL-4) and gamma interferon (IFN-γ) in airway remodeling in patients with chronic obstructive pulmonary disease (COPD). Methods From December 2017 to August 2018, lung tissue was collected from the Department of Thoracic Surgery, Central South University, Xiangya School of Medical, Affiliated Haikou Hospital. Lung tissue samples from 16 patients with lung cancer and 12 patients with lung cancer combined with COPD were surgically removed. Lung fibroblasts were isolated and identified from normal lung tissues and lung tissues of COPD patients, respectively, and the expression levels of hypoxia-induced factor 1α (HIF-1α) and transformed growth factor β1 (TGF-β1) were detected by qRT-PCR and Western blot, lung fibroblasts were stimulated with IL-4 and IFN-γ, respectively, and the expression levels of HIF-1α and TGF-β1 were subsequently detected to evaluate the effects of IL-4 and IFN-γ on lung fibroblasts HIF-1α/TGF-β1. Results Compared with normal lung fibroblasts, mRNA levels of HIF-1α and TGF-β1 in lung fibroblasts of COPD patients were significantly increased (P ＜ 0.01). IL-4 induced increased expression of HIF-1α and TGF-β1 in lung fibroblasts (P ＜ 0.05). The expression of HIF-1α and TGF-β1 was positively correlated with the duration of IL-4 action （R2 = 0.8736，P = 0.0018；R2 = 0.8637，P = 0.0223）. IFN-γ inhibits HIF-1α and TGF-β1 expression in lung fibroblasts (P ＜ 0.05), the expression of HIF-1α and TGF-β1 was negatively correlated with IFN-gamma duration （R2 = 0.8410，P = 0.0283；R2 = 0.8142，P = 0.0361）. Conclusion IL-4 promoted the expression of HIF-1α and TGF-β1 in pulmonary fibroblasts in COPD patients. Moreover, the expression of HIF-1α and TGF-β1 was positively correlated with the duration of IL-4 action. In contrast, IFN-γ inhibited the expression of HIF-1α and TGF-β1 in pulmonary fibroblasts in COPD patients, and the expression of HIF-1α and TGF-β1 was negatively correlated with the duration of IFN-γ action.

Key words： Interleukin 4 Interferon-γ Hypoxia-induced factor 1α Transformed growth factor β1 Chronic obstructive pulmonary disease remodeling

基金资助:海南省基础与应用基础研究计划（省自然科学基金）项目（818MS137）。

作者简介: 曾慈梅（1972-），女，硕士，副主任医师，主要从事COPD的基础与临床研究。

引用本文:

曾慈梅1 欧宗兴1 黄邓高2 沈彬1 王蕾1 马西淼3 曹卉2. IL-4和IFN-γ对COPD患者肺成纤维细胞HIF-1α和TGF-β1表达的影响[J]. 中国医药导报, 2019, 16(29): 16-20.
ZENG Cimei1 OU Zongxing1 HUANG Denggao2 SHEN Bing1 WANG Lei1 MA Ximiao3 CAO Hui2. Effect of IL-4 and IFN-γ on the expression of HIF-1α and TGF-β1 in lung fibroblasts of COPD patients. 中国医药导报, 2019, 16(29): 16-20.

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[1] Mantoani LC，Rubio N，McKinstry B，et al. Interventions to modify physical activity in patients with COPD：a systematic review [J]. Eur Respir J，2016，48（1）：69-81.
[2] Wei B，Sheng LC. Changes in Th1/Th2-producing cytokines during acute exacerbation chronic obstructive pulmonary disease [J]. J Int Med Res，2018，46（9）：3890-3902.
[3] 孙芳，石红梅，韩俊垒，等.慢性阻塞性肺疾病急性加重期患者IFN-γ与IL-4的变化及意义[J].河南医学研究，2011，20（2）：141-143.
[4] Mandal J，Roth M，Papakonstantinou E，et al. Adrenomedullin mediates pro-angiogenic and pro-inflammatory cytokines in asthma and COPD [J]. Pulm Pharmacol Ther，2019，56：8-14.
[5] Vitenberga Z，Pilmane M，Babjoni?觢eva A. The evaluation of inflammatory，anti-inflammatory and regulatory factors contributing to the pathogenesis of COPD in airways [J]. Pathol Res Pract，2019，215（1）：97-105.
[6] 蒋永亮，聂金，刘蕾，等.ING4、PHDs以及HIF-1α在低氧性肺动脉高压大鼠中的表达变化[J].中国组织化学与细胞化学杂志，2014，23（2）：117-124.
[7] Fu X，Zhang F. Role of the HIF-1 signaling pathway in chronic obstructive pulmonary disease [J]. Exp Ther Med，2018，16（6）：4553-4561.
[8] Aghasafari P，George U，Pidaparti R. A review of inflammatory mechanism in airway diseases [J]. Inflamm Res，2019，68（1）：59-74.
[9] Kruse C，Pesek B，Anderson M，et al. Telemonitoring to Manage Chronic Obstructive Pulmonary Disease：Systematic Literature Review [J]. JMIR Med Inform，2019，7（1）：e11496.
[10] Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease [J]. Nat Rev Immunol，2018，18（7）：454-466.
[11] Barnes PJ. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease [J]. J Allergy Clin Immunol，2016，138（1）：16-27.
[12] 姜国伟，刘建红，吴冠仪.慢性阻塞性肺疾病患者IFN-γ、IL-4血清水平变化及临床意义[J].中国农村卫生事业管理，2014，34（7）：903-904.
[13] Barnes PJ. Cellular and molecular mechanisms of asthma and COPD [J]. Clin Sci （Lond），2017，131（13）：1541-1558.
[14] Zhang HX，Yang JJ，Zhang SA，et al. HIF-1α promotes inflammatory response of chronic obstructive pulmonary disease by activating EGFR/PI3K/AKT pathway [J]. Eur Rev Med Pharmacol Sci，2018，22（18）：6077-6084.
[15] Kang MH，Oh SC，Lee HJ，et al. Metastatic function of BMP-2 in gastric cancer cells：the role of PI3K/AKT，MAPK，the NF-κB pathway，and MMP-9 expression [J]. Exp Cell Res，2011，317（12）：1746-1762.
[16] Mahmood MQ，Reid D，Ward C，et al. Transforming growth factor （TGF） β1 and Smad signalling pathways：A likely key to EMT-associated COPD pathogenesis [J]. Respirology，2017，22（1）：133-140.
[17] Shibata S，Miyake K，Tateishi T，et al. Basophils trigger emphysema development in a murine model of COPD through IL-4-mediated generation of MMP-12-producing macrophages [J]. Proc Natl Acad Sci USA，2018，115（51）：13057-13062.
[18] Mitra A，Vishweswaraiah S，Thimraj TA，et al. Association of Elevated Serum GM-CSF，IFN-γ，IL-4，and TNF-α Concentration with Tobacco Smoke Induced Chronic Obstructive Pulmonary Disease in a South Indian Population [J]. Int J Inflam，2018，2018：2027856.
[19] Huang AX，Lu LW，Liu WJ，et al. Plasma Inflammatory Cytokine IL-4，IL-8，IL-10，and TNF-α Levels Correlate with Pulmonary Function in Patients with Asthma-Chronic Obstructive Pulmonary Disease （COPD） Overlap Syndrome [J]. Med Sci Monit，2016，22：2800-2808.
[20] Yin T，Zhu Z，Mei Z，et al. Analysis of viral infection and biomarkers in patients with acute exacerbation of chronic obstructive pulmonary disease [J]. Clin Respir J，2018， 12（3）：1228-1239.