Changes of Cytokines in Bronchoalveolar Lavage Fluid in Rats Exposed to Paraquat_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZhangZhijian , PengLibo , DongYaoyao ,  LuoWanyun

Department of Critical Care Medicine, People's Hospital of Ba'nan District, Chongqing, 401320, China;

Corresponding author：

LuoWanyun, Email: lwybnyy@yeah.net

Keywords：

Paraquat; Rats; Bronchoalveolar lavage fluid; Interleukin; Macrophage inflammatory protein; Monocyte chemoattractant protein; Biopterin

DOI：

10.7507/1671-6205.2015045

Video：

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Objective To investigate the changes of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to paraquat (PQ). Methods Adult healthy SD rats were randomly divided into a control group (n=8) and three experimental groups (PQ in low dosage of 15 mg/kg,medium dosage of 30 mg/kg,and high dosage of 60 mg/kg,n=24 in each group). The rats in three experimental groups were intragastrically administered with PQ,and the rats in the control group were treated with saline by gavage. Two rats in the control group and six rats in three experimental groups were sacrificed on 1^st,7^th,14^th,and 21^st day after exposure respectively. BALF was collected for measurement of interleukin-1(IL-1),IL-6,macrophage inflammatory protein-2(MIP-2),monocyte chemoattractant protein-1(MCP-1),and biopterin by ELISA. Results The levels of cytokines in all experimental groups were higher than those in the control group at any time point. In the exposure day 1 to day 14, IL-1 and biopterin levels in BALF increased significantly with the increase in PQ dose. On 14^th and 21^st day,IL-6 level in BALF increased significantly with the increase in PQ dosage. The levels of IL-1,IL-6,and biopterin in the experimental groups reached the peak on 14^th day. On 14^th day,the MIP-2 level in BALF of high-dosage group was significantly higher than that of low-dosage and medium-dosage groups (all P<0.05). The level of MCP-1 in the low-dosage group was lower than that in the medium-dosage and high-dosage groups at any time point (P<0.05). Conclusion IL-1,IL-6,MIP-2,MCP-1,and biopterin may play important roles in the development and progression of PQ-induce lung inflammation.

Citation： ZhangZhijian, PengLibo, DongYaoyao, LuoWanyun. Changes of Cytokines in Bronchoalveolar Lavage Fluid in Rats Exposed to Paraquat. Chinese Journal of Respiratory and Critical Care Medicine, 2015, 14(2): 178-181. doi: 10.7507/1671-6205.2015045 Copy

1.	Inokuchi Y,Nakajima Y,Shimazawa M,et al. Effect of an inducer of Bip,a molecular chaperone,on endoplasmic reticulum(ER) stress-induced retinal cell death.Invest Ophthalmol Vis Sci,2009,50:334-344.
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4.	张志坚,董瑶瑶,李晓萍,等.沙苑子总黄酮通过抑制内质网应激和JNK通路过度活化减轻百草枯中毒大鼠肺损伤.中华危重病急救医学,2014,26:383-387.
5.	张志坚,董瑶瑶,吴灿,等.百草枯致大鼠肺纤维化肺组织内质网相关凋亡基因Caspase-12的表达.中国呼吸与危重监护杂志,2014,13:268-272.
6.	张慧利,柳远飞,罗序睿,等.氢气饱和生理盐水对百草枯中毒大鼠肺组织的作用.中华急诊医学杂志,2011,20:708-711.
7.	Ozeki N,Kawai R,Yamaguchi H,et al. IL-1β-induced matrix metalloproteinase-13 is activated by a disintegrin and metalloprotease-28-regulated proliferation of human osteoblast-like cells. Exp Cell Res,2014,15,323:165-177.
8.	Klueh U,Antar O,Qiao Y,et al.Role of interleukin-1/interleukin-1 receptor antagonist family of cytokines in long-term continuous glucose monitoring in vivo. J Diabetes Sci Technol,2013,7:1538-1546.
9.	Erta M,Quintana A,Hidalgo J. Interleukin-6,a major cytokine in the central nervous system. Int J Biol Sci,2012,8:1254-1266.
10.	Robak E,Kulczycka-Siennicka L,Gerlicz Z,et al. Correlations between concentrations of interleukin (IL)-17A,IL-17B and IL-17F,and endothelial cells and proangiogenic cytokines in systemic lupus erythematosus patients.Eur Cytokine Netw,2013,24:60-68.
11.	Miao JW,Liu LJ,Huang J. Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma. Int J Oncol, 2014,45:165-176.
12.	Sozer V,Himmetoglu S,Korkmaz GG,et al. Paraoxonase,oxidized low density lipoprotein,monocyte chemoattractant protein-1 and adhesion molecules are associated with macrovascular complications in patients with type 2 diabetes mellitus. Minerva Med,2014,105:237-244.
13.	Avasarala S,Zhang F,Liu G,et al. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome. PLoS One, 2013,8:e57285.
14.	Fu PK,Yang CY,Tsai TH,et al. Moutan cortex radicis improves lipopolysaccharide-induced acute lung injury in rats through anti-inflammation. Phytomedicine,2012,19:1206-1215.
15.	Zhou GX,Zhu XJ,Ding XL,et al. Protective effects of MCP-1 inhibitor on a rat model of severe acute pancreatitis. Hepatobiliary Pancreat Dis Int,2010,9:201-207.
16.	Toygar M,Aydin I,Agilli M,et al. The relation between oxidative stress,inflammation,and neopterin in the paraquat-induced lung toxicity. Hum Exp Toxicol,2014,12:1-7.
17.	Uyar IS,Onal S,Uysal A,et al. Evaluation of systemic inflammatory response in cardiovascular surgery via interleukin-6,interleukin-8,and neopterin. Heart Surg Forum,2014,17:E13-E17.

1. Inokuchi Y,Nakajima Y,Shimazawa M,et al. Effect of an inducer of Bip,a molecular chaperone,on endoplasmic reticulum(ER) stress-induced retinal cell death.Invest Ophthalmol Vis Sci,2009,50:334-344.
2. Dinis-Oliveira RJ,Duarte JA,Sanchez-Navarro A,et al. Paraquat poisonings:mechanisms of lung toxicity,clinical features,and treatment.Crit Rev Toxicol,2008,38:13-71.
3. Ranieri M,Brajkovic S,Riboldi G,et al. Mitochondrial fusion proteins and human diseases. Neurol Res Int,2013,2013:293893.
4. 张志坚,董瑶瑶,李晓萍,等.沙苑子总黄酮通过抑制内质网应激和JNK通路过度活化减轻百草枯中毒大鼠肺损伤.中华危重病急救医学,2014,26:383-387.
5. 张志坚,董瑶瑶,吴灿,等.百草枯致大鼠肺纤维化肺组织内质网相关凋亡基因Caspase-12的表达.中国呼吸与危重监护杂志,2014,13:268-272.
6. 张慧利,柳远飞,罗序睿,等.氢气饱和生理盐水对百草枯中毒大鼠肺组织的作用.中华急诊医学杂志,2011,20:708-711.
7. Ozeki N,Kawai R,Yamaguchi H,et al. IL-1β-induced matrix metalloproteinase-13 is activated by a disintegrin and metalloprotease-28-regulated proliferation of human osteoblast-like cells. Exp Cell Res,2014,15,323:165-177.
8. Klueh U,Antar O,Qiao Y,et al.Role of interleukin-1/interleukin-1 receptor antagonist family of cytokines in long-term continuous glucose monitoring in vivo. J Diabetes Sci Technol,2013,7:1538-1546.
9. Erta M,Quintana A,Hidalgo J. Interleukin-6,a major cytokine in the central nervous system. Int J Biol Sci,2012,8:1254-1266.
10. Robak E,Kulczycka-Siennicka L,Gerlicz Z,et al. Correlations between concentrations of interleukin (IL)-17A,IL-17B and IL-17F,and endothelial cells and proangiogenic cytokines in systemic lupus erythematosus patients.Eur Cytokine Netw,2013,24:60-68.
11. Miao JW,Liu LJ,Huang J. Interleukin-6-induced epithelial-mesenchymal transition through signal transducer and activator of transcription 3 in human cervical carcinoma. Int J Oncol, 2014,45:165-176.
12. Sozer V,Himmetoglu S,Korkmaz GG,et al. Paraoxonase,oxidized low density lipoprotein,monocyte chemoattractant protein-1 and adhesion molecules are associated with macrovascular complications in patients with type 2 diabetes mellitus. Minerva Med,2014,105:237-244.
13. Avasarala S,Zhang F,Liu G,et al. Curcumin modulates the inflammatory response and inhibits subsequent fibrosis in a mouse model of viral-induced acute respiratory distress syndrome. PLoS One, 2013,8:e57285.
14. Fu PK,Yang CY,Tsai TH,et al. Moutan cortex radicis improves lipopolysaccharide-induced acute lung injury in rats through anti-inflammation. Phytomedicine,2012,19:1206-1215.
15. Zhou GX,Zhu XJ,Ding XL,et al. Protective effects of MCP-1 inhibitor on a rat model of severe acute pancreatitis. Hepatobiliary Pancreat Dis Int,2010,9:201-207.
16. Toygar M,Aydin I,Agilli M,et al. The relation between oxidative stress,inflammation,and neopterin in the paraquat-induced lung toxicity. Hum Exp Toxicol,2014,12:1-7.
17. Uyar IS,Onal S,Uysal A,et al. Evaluation of systemic inflammatory response in cardiovascular surgery via interleukin-6,interleukin-8,and neopterin. Heart Surg Forum,2014,17:E13-E17.

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Changes of Cytokines in Bronchoalveolar Lavage Fluid in Rats Exposed to Paraquat

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