Anti-inflammatory effects of apocynin, an inhibitor of NADPH oxidase, in airway inflammation
So Yong Kim
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorKeun-Ai Moon
Division of Allergy, University of Ulsan College of Medicine, Seoul, Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorHee-Yeon Jo
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorSookyung Jeong
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Search for more papers by this authorSeung-Han Seon
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Search for more papers by this authorEunyu Jung
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Search for more papers by this authorYou Sook Cho
Division of Allergy, University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorCorresponding Author
Eunyoung Chun
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Current address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Dr K-Y Lee, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea. E-mail: [email protected]
Dr E Chun, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300, Cheoncheon-dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, Republic of KoreaM. E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Ki-Young Lee
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Dr K-Y Lee, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea. E-mail: [email protected]
Dr E Chun, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300, Cheoncheon-dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, Republic of KoreaM. E-mail: [email protected]
Search for more papers by this authorSo Yong Kim
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorKeun-Ai Moon
Division of Allergy, University of Ulsan College of Medicine, Seoul, Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorHee-Yeon Jo
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
These authors contributed equally to this work.
Search for more papers by this authorSookyung Jeong
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Search for more papers by this authorSeung-Han Seon
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Search for more papers by this authorEunyu Jung
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Search for more papers by this authorYou Sook Cho
Division of Allergy, University of Ulsan College of Medicine, Seoul, Republic of Korea
Search for more papers by this authorCorresponding Author
Eunyoung Chun
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Current address: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Dr K-Y Lee, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea. E-mail: [email protected]
Dr E Chun, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300, Cheoncheon-dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, Republic of KoreaM. E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Ki-Young Lee
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea
Dr K-Y Lee, Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Republic of Korea. E-mail: [email protected]
Dr E Chun, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300, Cheoncheon-dong, Jangan-Gu, Suwon, Gyeonggi-Do 440-746, Republic of KoreaM. E-mail: [email protected]
Search for more papers by this authorAbstract
Oxidative stress is implicated in the pathogenesis of allergic asthma and remains an attractive target for the prevention of the disease. Herein, we investigated the anti-inflammatory effects of apocynin, a NADPH oxidase (NOX) inhibitor, in both in vitro and in vivo allergen-induced experimental asthma mediated by Th2 hyperresponsiveness. Apocynin showed potential antioxidant activities and inhibitory effects on the activation of redox-sensitive transcription factors, such as NF-κB and AP-1, induced by pro-inflammatory stimuli, such as TNF-α, lipopolysaccharide and Poly I:C, and that inhibited the production of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6. In in vivo experimental asthma model, moreover, apocynin significantly attenuated ovalbumin-induced airway hyperresponsiveness and inflammation, as shown by the attenuation of total inflammatory cell and soluble product influx into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-4, IL-5, IL-12, IL-13 and TNF-α. Apocynin also significantly reduced lung inflammation in the tissues. Altogether, these results suggest that apocynin may be useful in the treatment of inflammatory diseases induced by oxidative stress through NOX activity.
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References
- 1Busse WW, Lemanske RF. Asthma. N Engl J Med 2001; 344: 350–362.
- 2Humbles AA, Lloyd CM, McMillan SJ, Friend DS, Xanthou G, McKenna EE et al. A critical role for eosinophils in allergic airways remodeling. Science 2004; 305: 1776–1779.
- 3Kim TB, Kim SY, Moon KA, Park CS, Jang MK, Yun ES et al. Five-aminoimidazole-4-carboxamide-1-beta-4 ribofuranoside attenuates poly (I:C)-induced airway inflammation in a murine model of asthma. Clin Exp Allergy 2007; 37: 1709–1719.
- 4Renz H. Soluble interleukin-4 receptor (sIL-4R) in allergic diseases. Inflamm Res 1999; 48: 425–431.
- 5Chung KF, Barnes PJ. Cytokines in asthma. Thorax 1999; 54: 825–857.
- 6Rahman I, MacNee W. Oxidative stress and regulation of glutathione in lung inflammation. Eur Respir J 2000; 16: 534–554.
- 7Dworski R. Oxidant stress in asthma. Thorax 2000; 55: S51–S53.
- 8Rahman I. Oxidative stress, chromatin remodeling and gene transcription in inflammation and chronic lung diseases. J Biochem Mol Biol 2003; 36: 95–109.
- 9Barnes PJ. Reactive oxygen species and airway inflammation. Free Radic Biol Med 1990; 9: 235–243.
- 10Henricks PA, Nijkamp FP. Reactive oxygen species as mediators in asthma. Pulm Pharmacol Ther 2001; 14: 409–420.
- 11Andreadis AA, Hazen SL, Comhair SA, Erzurum SC. Oxidative and nitrosative events in asthma. Free Radic Biol Med 2003; 35: 213–225.
- 12Williams CM, Galli SJ. Mast cells can amplify airway reactivity and features of chronic inflammation in an asthma model in mice. J Exp Med 2000; 192: 455–462.
- 13Elias JA, Lee CG, Zheng T, Ma B, Homer RJ, Zhu Z. New insights into the pathogenesis of asthma. J Clin Invest 2003; 111: v291–v297.
- 14Akdis CA. Allergy and hypersensitivity: mechanisms of allergic disease. Curr Opin Immunol 2006; 18: 718–726.
- 15Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med 2006; 355: 2226–2235.
- 16Umetsu DT, Dekruyff RH. Immune dysregulation in asthma. Curr Opin Immunol 2006; 18: 727–732.
- 17Adler V, Yin Z, Tew KD, Ronai Z. Role of redox potential and reactive oxygen species in stress signalling. Oncogene 1999; 18: 6104–6111.
- 18Haddad JJ. Antioxidant and prooxidant mechanisms in the regulation of redox(y)-sensitive transcription factors. Cell Signal 2002; 14: 879–897.
- 19Miller AA, Drummond GR, Sobey CG. Reactive oxygen species in the cerebral circulation: are they all bad? Antioxid Redox Signal 2006; 8: 1113–1120.
- 20Babior BM. NADPH oxidase: an update. Blood 1999; 93: 1464–1476.
- 21Griendling KK, Harrison DG. Dual role of reactive oxygen species in vascular growth. Circ Res 1999; 85: 562–563.
- 22Van Heerebeek L, Meischl C, Stooker W, Meijer CJ, Niessen HW, Roos D. NADPH oxidase(s): new source(s) of reactive oxygen species in the vascular system? J Clin Pathol 2002; 55: 561–568.
- 23Ogawa Y, Kobayashi T, Nishioka A, Kariya S, Hamasato S, Seguchi H et al. Radiation-induced oxidative DNA damage, 8-oxoguanine, in human peripheral T cells. Int J Mol Med 2003; 11: 27–32.
- 24Genova ML, Pich MM, Bernacchia A, Bianchi C, Biondi A, Bovina C et al. The mitochondrial production of reactive oxygen species in relation to aging and pathology. Ann NY Acad Sci 2004; 1011: 86–100.
- 25Davies KJ. The broad spectrum of responses to oxidants in proliferating cells: a new paradigm for oxidative stress. IUBMB Life 1999; 48: 41–47.
- 26Lee YJ, Shacter E. Oxidative stress inhibits apoptosis in human lymphoma cells. J Biol Chem 1999; 274: 19792–19798.
- 27Aslan M, Ozben T. Oxidants in receptor tyrosine kinase signal transduction pathways. Antioxid Redox Signal 2003; 5: 781–788.
- 28Tonks NK. Redox redux: revisiting PTPs and the control of cell signalling. Cell 2005; 121: 667–670.
- 29Hougee S, Hartog A, Sanders A, Graus YM, Hoijer MA, Garssen J et al. Oral administration of the NADPH-oxidase inhibitor apocynin partially restores diminished cartilage proteoglycan synthesis and reduces inflammation in mice. Eur J Pharmacol 2006; 531: 264–269.
- 30Johnson DK, Schillinger KJ, Kwait DM, Hughes CV, McNamara EJ, Ishmael F et al. Inhibition of NADPH oxidase activation in endothelial cells by ortho-methoxy-substituted catechols. Endothelium 2002; 9: 191–203.
- 31Stolk J, Hiltermann TJN, Dijkman JH, Verhoeven AJ. Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol. Am J Respir Cell Mol Biol 1994; 11: 95–102.
- 32Muijsers RB, van Den Worm E, Folkerts G, Beukelman CJ, Koster AS, Postma DS et al. Apocynin inhibits peroxynitrite formation by murine macrophages. Br J Pharmacol 2000; 130: 932–936.
- 33Sadeghi-Hashjin G, Folkerts G, Henricks PA, Verheyen AK, van der Linde HJ, van Ark I et al. Peroxynitrite induces airway hyperresponsiveness in guinea pigs in vitro and in vivo. Am J Respir Crit Care Med 1996; 153: 1697–1701.
- 34Chen CC, Chow MP, Huang WC, Lin YC, Chang YJ. Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion mole- cule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure–activity relationships. Mol Pharmacol 2004; 66: 683–693.
- 35Wang T, Zhang X, Li JJ. The role of NF-kappaB in the regulation of cell stress responses. Int Immunopharmacol 2002; 2: 1509–1520.
- 36Peters EA, Hiltermann JT, Stolk J. Effect of apocynin on ozone-induced airway hyperresponsiveness to methacholine in asthmatics. Free Radic Biol Med 2001; 31: 1442–1447.
- 37MacFarlane PM, Satriotomo I, Windelborn JA, Mitchell GS. NADPH oxidase activity is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation. J Physiol 2009; 587: 1931–1942.
- 38Coyoy A, Valencia A, Guemez-Gamboa A, Morán J. Role of NADPH oxidase in the apoptotic death of cultured cerebellar granule neurons. Free Radic Biol Med 2008; 45: 1056–1064.
- 39Kim SY, Kim TB, Moon KA, Kim TJ, Shin D, Cho YS et al. Regulation of pro-inflammatory responses by lipoxygenases via intracellular reactive oxygen species in vitro and in vivo. Exp Mol Med 2008; 40: 461–476.
- 40Heumüller S, Wind S, Barbosa-Sicard E, Schmidt HH, Busse R, Schröder K et al. Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 2008; 51: 211–217.
- 41Impellizzeri D, Esposito E, Mazzon E, Paterniti I, Di Paola R, Bramanti P et al. Effect of apocynin, a NADPH oxidase inhibitor, on acute lung inflammation. Biochem Pharmacol 2011; 81: 636–648.