Phosphatidylinositol 3-kinase inhibitor suppresses inducible nitric oxide synthase expression in bronchiole epithelial cells in asthmatic rats
作者： Xiaodong Xia , Xiaoguang Hu , Hui Xu , Liqin Wu , Yuanrong Dai
DOI: 10.1007/S11010-011-1023-Y
关键词:
摘要: Inducible nitric oxide synthase (iNOS) is known to produce (NO), which a main contributor asthmatic airway inflammation. Recent studies have shown that phosphatidylinositol 3-kinase (PI3K) ubiquitously expressed in epithelial cells and its inhibition could relieve inflammation hyperresponsiveness. This study aimed explore the interaction of PI3K NO signaling allergic asthma. We investigated effects inhibitor wortmannin on iNOS expression bronchiole NO, IL-4 IFN-γ levels lung tissues rat model, was prepared by 10% OVA solution sensitization 1% aerosol challenge. Our results showed ratio eosinophils total BALF, activity, increased after challenge, but then attenuated administration wortmannin. In contrast, level decreased challenge The protein cells, mRNA activity markedly upregulated upregulation significantly antagonized Taken together, these data provide evidence functions upstream modulate iNOS/NO signaling, promotes development animal model. lead reduced production, therefore inhibiting inflammatory responses.
springer.com
sci-hub.se 参考文章(36)
David Chantry, Anne Vojtek, Adam Kashishian, Douglas A. Holtzman, Christi Wood, Patrick W. Gray, Jonathan A. Cooper, Merl F. Hoekstra, p110δ, a Novel Phosphatidylinositol 3-Kinase Catalytic Subunit That Associates with p85 and Is Expressed Predominantly in Leukocytes Journal of Biological Chemistry. ,vol. 272, pp. 19236- 19241 ,(1997) , 10.1074/JBC.272.31.19236
Yoshiyuki Hattori, Sachiko Hattori, Kikuo Kasai, Lipopolysaccharide activates Akt in vascular smooth muscle cells resulting in induction of inducible nitric oxide synthase through nuclear factor-kappa B activation. European Journal of Pharmacology. ,vol. 481, pp. 153- 158 ,(2003) , 10.1016/J.EJPHAR.2003.09.034
Vanessa Pinho, Danielle G Souza, Michele M Barsante, Fabiana P Hamer, Marta S De Freitas, Adriano G Rossi, Mauro M Teixeira, None, Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation. Journal of Leukocyte Biology. ,vol. 77, pp. 800- 810 ,(2005) , 10.1189/JLB.0704386
Jennifer M. Bratt, Lisa M. Franzi, Angela L. Linderholm, Michael S. Last, Nicholas J. Kenyon, Jerold A. Last, Arginase enzymes in isolated airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin. Toxicology and Applied Pharmacology. ,vol. 234, pp. 273- 280 ,(2009) , 10.1016/J.TAAP.2008.10.007
Bart Vanhaesebroeck, Khaled Ali, Antonio Bilancio, Barbara Geering, Lazaros C. Foukas, Signalling by PI3K isoforms: insights from gene-targeted mice. Trends in Biochemical Sciences. ,vol. 30, pp. 194- 204 ,(2005) , 10.1016/J.TIBS.2005.02.008
Kyung S. Lee, Ho K. Lee, Joel S. Hayflick, Yong C. Lee, Kamal D. Puri, Inhibition of phosphoinositide 3-kinase δ attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model The FASEB Journal. ,vol. 20, pp. 455- 465 ,(2006) , 10.1096/FJ.05-5045COM
Carla M Prado, Edna A Leick-Maldonado, Larissa Yano, Adriana S Leme, Vera L Capelozzi, Milton A Martins, Iolanda FLC Tiberio, None, Effects of nitric oxide synthases in chronic allergic airway inflammation and remodeling. American Journal of Respiratory Cell and Molecular Biology. ,vol. 35, pp. 457- 465 ,(2006) , 10.1165/RCMB.2005-0391OC
Shang-Jyh Kao, Hui-Chieh Lei, Chen-Tzu Kuo, Ming-Shyan Chang, Bing-Chang Chen, Yau-Chong Chang, Wen-Ta Chiu, Chien-Huang Lin, Lipoteichoic acid induces nuclear factor-κB activation and nitric oxide synthase expression via phosphatidylinositol 3-kinase, Akt, and p38 MAPK in RAW 264.7 macrophages Immunology. ,vol. 115, pp. 366- 374 ,(2005) , 10.1111/J.1365-2567.2005.02160.X
Jingjing Jiang, Nikita Malavia, Vinod Suresh, Steven C George, Nitric oxide gas phase release in human small airway epithelial cells Respiratory Research. ,vol. 10, pp. 3- 3 ,(2009) , 10.1186/1465-9921-10-3
Wei Duan, Ana M.K. Aguinaldo Datiles, Bernard P. Leung, Chris J. Vlahos, W.S. Fred Wong, An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model. International Immunopharmacology. ,vol. 5, pp. 495- 502 ,(2005) , 10.1016/J.INTIMP.2004.10.015