Effects of Tobacco Smoke Exposure on HDAC2,IL-8 and TNF-α Expression in Peripheral Blood of Patients with Lung Adenocarcinoma_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YaoLunkai ,  LiuGuangnan , HuangSiming , LiWentao , LiYu

Department of Respiratory Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China;

Corresponding author：

LiuGuangnan, Email: gnliu63@hotmail.com

Keywords：

Lung adenocarcinoma; Histone deacetylase 2; Interleukin-8; Tumor necrosis factor-α; Tobacco smoke exposure

DOI：

10.7507/1671-6205.2016085

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Objective To investigate the effects of tobacco smoke exposure on histone deacetylase 2 (HDAC2),interleukin-8(IL-8)and tumor necrosis factor-α(TNF-α)expression in peripheral blood of patients with lung adenocarcinoma and analyze the relationships among them. Methods Seventy-three cases diagnosed as lung adenocarcinoma were collected in the First Affiliated Hospital and Affiliated Tumor Hospital of Guangxi Medical University from April 2014 to March 2015.All patients underwent lung function test preoperatively.Fourteen healthy volunteers without tobacco smoke exposure and chronic obstructive pulmonary disease (COPD)were recruited as healthy control.According to the lung function and tobacco smoke exposure,all cases were divided into four groups,ie. a healthy control group (group A,14 cases),a group without tobacco smoke exposure and COPD(group B,19 cases),a group with tobacco smoke exposure and without COPD(group C,33 cases),and a group with tobacco smoke exposure and COPD(group D,21 cases).The expressions of HDAC2 mRNA,IL-8 mRNA and TNF-α mRNA in peripheral blood mononuclear cells (PBMCs)were detected by real-time polymerase chain reaction (PCR).The contents of IL-8 and TNF-α in serum were detected by ELISA. Results Compared with group A,the HDAC2 mRNA expression in PBMCs had no difference in group B(P>0.05),and was down-regulated significantly in group C and D (P<0.05),which in group D was the most obvious.Compared with group A,the expressions of IL-8 mRNA and TNF-α mRNA in PBMCs and the contents of IL-8 and TNF-α in serum were significantly higher in all lung adenocarcinoma patients(all P<0.05),and the up-regulation was more obvious in group D.The relative expression of HDAC2 mRNA in PBMCs showed no significant difference with respect to age,gender or TNM stage (P>0.05).IL-8 and TNF-α in PBMCs and serum showed no significant difference with respect to age and gender (P>0.05),and were higher in the patients with TNM stage Ⅲ lung adenocarcinoma than those with stage Ⅰ and Ⅱ(P<0.05),with no obvious difference between stage Ⅰ and stage Ⅱ (P>0.05). Conclusion Tobacco smoke exposure causes lower expression of HDAC2 and over-expression of IL-8 and TNF-α in peripheral blood of patients with lung adenocarcinoma,can aggravate inflammatory response especially when complicated with COPD,which may be related to the prognosis of lung adenocarcinoma.

Citation： YaoLunkai, LiuGuangnan, HuangSiming, LiWentao, LiYu. Effects of Tobacco Smoke Exposure on HDAC2,IL-8 and TNF-α Expression in Peripheral Blood of Patients with Lung Adenocarcinoma. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(4): 361-364. doi: 10.7507/1671-6205.2016085 Copy

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15.	Sekine Y,Yamada Y,Chiyo M,et al.Association of chronic obstructive pulmonary disease and tumor recurrence in patients with stage IA lung cancer after complete resection.Ann Thorac Surg,2007,84:946-950.
16.	秦茵茵, 周承志,张筱娴,等.原发性支气管肺癌合并慢性阻塞性肺疾病患者的临床研究.中国呼吸与危重监护杂志,2013,12:65-68.

1. 孙琼, 焦顺昌.非小细胞肺癌疫苗治疗的现状.解放军医学院学报,2014,35:398-401.
2. Fan X,Zhang X,Wang H,et al.Reevaluation of survival and prognostic factors in pathologic stage I lung adenocarcinoma by the new 2009 TNM classification.Tumour Biol,2014,35:5905-5910.
3. Scott HR,McMillan DC,Forrest LM,et al.The systemic inflammatory response,weight loss,performance status and survival in patients with inoperable non-small cell lung cancer.Br J Cancer,2002,87:264-267.
4. 傅钰雁, 柳广南,黄斯明,等.红霉素对氧化应激下A549细胞的影响.广东医学,2014,35:340-344.
5. Detterbeck FC,Boffa DJ,Tanoue LT.The new lung cancer staging system.Chest,2009,136:260-271.
6. 杨功焕, 马杰民,刘娜,等.中国人群2002年吸烟和被动吸烟的现状调查.中华流行病学杂志,2005,26:77-83.
7. Adenuga D,Yao H,March TH,et al.Histone deacetylase 2 is phosphorylated,ubiquitinated,and degraded by cigarette smoke.Am J Respir Cell Mol Biol,2009,40:464-473.
8. Barnes PJ.Immunology of asthma and chronic obstructive pulmonary disease.Nat Rev Immunol,2008,8:183-192.
9. Ito K,Ito M,Elliott WM,et al.Decreased histone deacetylase activity in chronic obstructive pulmonary disease.N Engl J Med,2005,352:1967-1976.
10. 陈延伟, 杨炯.COPD患者外周血单核细胞中HDAC活性及其与肺功能和吸烟的关系.中国医药导报,2009,6:16-19.
11. 王冬梅, 李为民,李静,等.吸烟与肺癌关系的Meta分析.中国呼吸与危重监护杂志,2009,8:229-233.
12. 王振元, 张林,王者生,等.白细胞介素-8在肺癌中表达的临床意义.中华肿瘤杂志,2002,24:159.
13. Yodkeeree S,Pompimon W,Limtrakul P.Crebanine,an aporphine alkaloid,sensitizes TNF-alpha-induced apoptosis and suppressed invasion of human lung adenocarcinoma cells A549 by blocking NF-kappaB-regulated gene products.Tumour Biol,2014,35:8615-8624.
14. Parsons A,Daley A,Begh R,et al.Influence of smoking cessation after diagnosis of early stage lung cancer on prognosis:systematic review of observational studies with meta-analysis.BMJ,2010,340:b5569.
15. Sekine Y,Yamada Y,Chiyo M,et al.Association of chronic obstructive pulmonary disease and tumor recurrence in patients with stage IA lung cancer after complete resection.Ann Thorac Surg,2007,84:946-950.
16. 秦茵茵, 周承志,张筱娴,等.原发性支气管肺癌合并慢性阻塞性肺疾病患者的临床研究.中国呼吸与危重监护杂志,2013,12:65-68.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of Tobacco Smoke Exposure on HDAC2,IL-8 and TNF-α Expression in Peripheral Blood of Patients with Lung Adenocarcinoma

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