ROS/Src /JNK 信号通路在香烟诱导气道上皮细胞黏液高分泌中的作用_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

田川 ¹ , 李琪 ² ,  周向东 ²

Department of Respiratory Medicine, Nanchuan People’s Hospital. Nanchuan, Chongqing, 400582, China;

Corresponding author：

周向东, Email: zxd999@263.net

Keywords：

Mucin; Cigarette smoke; Reactive oxygen species; Src; JNK

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Objective To explore the role of ROS/ Src / JNK signaling pathway in cigarette smoke extract( CSE) -induced mucin ( MUC) 5AC production in A549 airway epithelial cells. Methods The A549 airway epithelial cells were cultured in medium with CSE, then treated with ROS scavenger DMTU, c-Jun Nterminal kinase( JNK) specific inhibitor SP600125, and Src kinase inhibitor PP2, respectively. The relative content of reactive oxygen species( ROS) were assayed by special kit. The levels of MUC5AC in culture medium, epidermal growth factor receptor( EGFR) , activated EGFR and MUC5AC mRNA in culture cells were detected with ELISA,Western Blot and RT-PCR, respectively. Results A dose-dependent increasing of ROS production in cells exposed to dilutions of cigarette smoke solution was detected. DMTU inhibited cigarette smoke-induced Src phosphorylation( P lt; 0. 05) . SP600125 reduced the expression of MUC5AC ( P lt; 0. 05) compared with the normal group. The activation of JNK was suppressed by Src specific inhibitor PP2( P lt; 0. 05) . Conclusion ROS/ Src / JNK signal cascade may play a particular role in MUC5AC expression of A549 cells induced by cigarette smoke.

Citation： 田川,李琪,周向东. ROS/Src /JNK 信号通路在香烟诱导气道上皮细胞黏液高分泌中的作用. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(2): 127-130. doi: Copy

1.	by Hydrogen Peroxide in Endothelial Cells Involves Src-dependent Epidermal Growth Factor Receptor Transactivation. J Biol Chem,2001, 276: 16045-16050.
2.	Psarras S, Caramori G, Contoli M, et al. Oxidants in asthma and in chronic obstructive pulmonary disease( COPD) . Curr Pharm Des,2005, 11: 2053-2062.
3.	Shao MX, Nakanaga T, Nadel JA. Cigarette smoke induces MUC5AC mucin overproduction via tumor necrosis factor-alpha-converting enzyme in human airway epithelial( NCI-H292 ) cells. Am J Physiol Lung Cell Mol Physiol, 2004, 287: L420-L427.
4.	Takeyama K, Jung B, Shim JJ, et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol, 2001, 280:L165-L172.
5.	周向东, 童瑾, 兰箭. 慢性阻塞性肺疾病患者气道黏蛋白分子表型的研究. 中华结核和呼吸杂志, 2002, 25: 437.
6.	YoshizumM, Abe JI, Haendeler J, et al. Src and Cas Mediate JNK Activation but Not ERK1 /2 and p38 Kinases by Reactive Oxygen Species. J Biol Chem, 2000, 275: 11706-11712.
7.	Nakamura Y, Romberger DJ, Tate L, et al. Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis. Am J Respir Crit Care Med, 1995, 151: 1497-1503.
8.	Ma C, Bower KA, Lin H, et al. The role of epidermal growth factor receptor in ethanol-mediated inhibition of activator protein-1 transactivaion. Biochem Pharmacol, 2005, 69 : 1785 -1794 .
9.	Pinkus R, Weiner LM, Daniel V. Role of oxidants and antioxidants in the induction of AP-1, NF-κB, and gutathione-s transferase gene expression. J Biol Chem, 1996, 271: 13422-13429.
10.	Chen K, Vita JA, Berk BC, et al. c-Jun N-terminal Kinase Activation.
11.	Meurer S, Pioch S, Gross S. Reactive Oxygen Species Induce Tyrosine Phosphorylation of and Src Kinase Recruitment to NOsensitive Guanylyl Cyclase. J Biol Chen, 2005, 280: 33149-33156.
12.	Li JD, Feng W, Gallup M. et al. Activation of NF-κB via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells. Proc Natl Acad Sci USA, 1998, 95: 5718-5723.

1. by Hydrogen Peroxide in Endothelial Cells Involves Src-dependent Epidermal Growth Factor Receptor Transactivation. J Biol Chem,2001, 276: 16045-16050.
2. Psarras S, Caramori G, Contoli M, et al. Oxidants in asthma and in chronic obstructive pulmonary disease( COPD) . Curr Pharm Des,2005, 11: 2053-2062.
3. Shao MX, Nakanaga T, Nadel JA. Cigarette smoke induces MUC5AC mucin overproduction via tumor necrosis factor-alpha-converting enzyme in human airway epithelial( NCI-H292 ) cells. Am J Physiol Lung Cell Mol Physiol, 2004, 287: L420-L427.
4. Takeyama K, Jung B, Shim JJ, et al. Activation of epidermal growth factor receptors is responsible for mucin synthesis induced by cigarette smoke. Am J Physiol Lung Cell Mol Physiol, 2001, 280:L165-L172.
5. 周向东, 童瑾, 兰箭. 慢性阻塞性肺疾病患者气道黏蛋白分子表型的研究. 中华结核和呼吸杂志, 2002, 25: 437.
6. YoshizumM, Abe JI, Haendeler J, et al. Src and Cas Mediate JNK Activation but Not ERK1 /2 and p38 Kinases by Reactive Oxygen Species. J Biol Chem, 2000, 275: 11706-11712.
7. Nakamura Y, Romberger DJ, Tate L, et al. Cigarette smoke inhibits lung fibroblast proliferation and chemotaxis. Am J Respir Crit Care Med, 1995, 151: 1497-1503.
8. Ma C, Bower KA, Lin H, et al. The role of epidermal growth factor receptor in ethanol-mediated inhibition of activator protein-1 transactivaion. Biochem Pharmacol, 2005, 69 : 1785 -1794 .
9. Pinkus R, Weiner LM, Daniel V. Role of oxidants and antioxidants in the induction of AP-1, NF-κB, and gutathione-s transferase gene expression. J Biol Chem, 1996, 271: 13422-13429.
10. Chen K, Vita JA, Berk BC, et al. c-Jun N-terminal Kinase Activation.
11. Meurer S, Pioch S, Gross S. Reactive Oxygen Species Induce Tyrosine Phosphorylation of and Src Kinase Recruitment to NOsensitive Guanylyl Cyclase. J Biol Chen, 2005, 280: 33149-33156.
12. Li JD, Feng W, Gallup M. et al. Activation of NF-κB via a Src-dependent Ras-MAPK-pp90rsk pathway is required for Pseudomonas aeruginosa-induced mucin overproduction in epithelial cells. Proc Natl Acad Sci USA, 1998, 95: 5718-5723.

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Chinese Journal of Respiratory and Critical Care Medicine

ROS/Src /JNK 信号通路在香烟诱导气道上皮细胞黏液高分泌中的作用

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