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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10.	陳延偉, 楊炯.COPD患者外周血單核細胞中HDAC活性及其與肺功能和吸煙的關系.中國醫藥導報,2009,6:16-19.
11.	王冬梅, 李為民,李靜,等.吸煙與肺癌關系的Meta分析.中國呼吸與危重監護雜志,2009,8:229-233.
12.	王振元, 張林,王者生,等.白細胞介素-8在肺癌中表達的臨床意義.中華腫瘤雜志,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,張筱嫻,等.原發性支氣管肺癌合并慢性阻塞性肺疾病患者的臨床研究.中國呼吸與危重監護雜志,2013,12:65-68.

1. 孫瓊, 焦順昌.非小細胞肺癌疫苗治療的現狀.解放軍醫學院學報,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. 傅鈺雁, 柳廣南,黃斯明,等.紅霉素對氧化應激下A549細胞的影響.廣東醫學,2014,35:340-344.
5. Detterbeck FC,Boffa DJ,Tanoue LT.The new lung cancer staging system.Chest,2009,136:260-271.
6. 楊功煥, 馬杰民,劉娜,等.中國人群2002年吸煙和被動吸煙的現狀調查.中華流行病學雜志,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. 陳延偉, 楊炯.COPD患者外周血單核細胞中HDAC活性及其與肺功能和吸煙的關系.中國醫藥導報,2009,6:16-19.
11. 王冬梅, 李為民,李靜,等.吸煙與肺癌關系的Meta分析.中國呼吸與危重監護雜志,2009,8:229-233.
12. 王振元, 張林,王者生,等.白細胞介素-8在肺癌中表達的臨床意義.中華腫瘤雜志,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,張筱嫻,等.原發性支氣管肺癌合并慢性阻塞性肺疾病患者的臨床研究.中國呼吸與危重監護雜志,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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