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Anti-inflammatory Effect of Arginase Inhibitor and Corticosteroid on Airway Allergic Reactions in a Dermatophogoides farinae-induced NC/Nga Mouse Model

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Abstract

The present study was aimed to investigate the effect of an arginase inhibitor, N-hydroxy-nor-l-arginine (nor-NOHA) and a corticosteroid, prednisolone, in an intranasal mite-induced NC/Nga mouse model of asthma. The treatment with nor-NOHA and prednisolone inhibited the increase in airway hyperresponsiveness, the number of bronchoalveolar lavage fluid cells, protein expression of arginase I and arginase II, messenger RNA (mRNA) expression of nitric oxide synthase (NOS)2 and Th2 cytokines such as interleukin (IL)-4, IL-5, and IL-13, and the pathological inflammatory changes of the lung. NOx levels in the lung were not changed in mice treated with prednisolone and elevated in mice treated with nor-NOHA or prednisolone plus nor-NOHA despite suppressed NOS2 mRNA expression. The study concluded that anti-inflammatory effect by nor-NOHA might be dependent on NO supply from depleted NO by downregulated arginine availability of arginase and was not related with the anti-inflammatory mechanisms by prednisolone.

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REFERENCES

  1. Ricciardolo, F.L., P.J. Sterk, B. Gaston, and G. Folkerts. 2004. Nitric oxide in health and disease of the respiratory system. Physiological Reviews 84: 731–765.

    Article  PubMed  CAS  Google Scholar 

  2. Que, L.G., L. Liu, Y. Yan, G.S. Whitehead, S.H. Gavett, D.A. Schwartz, and J.S. Stamler. 2005. Protection from experimental asthma by an endogenous bronchodilator. Science 308: 1618–1621.

    Article  PubMed  CAS  Google Scholar 

  3. Gaston, B., S. Sears, J. Woods, J. Hunt, M. Ponaman, T. McMahon, and J.S. Stamler. 1998. Bronchodilator S-nitrosothiol deficiency in asthmatic respiratory failure. Lancet 351: 1317–1319.

    Article  PubMed  CAS  Google Scholar 

  4. Que, L.G., Z. Yang, J.S. Stamler, N.L. Lugogo, and M. Kraft. 2009. S-nitrosoglutathione reductase: An important regulator in human asthma. American Journal of Respiratory and Critical Care Medicine 180: 226–231.

    Article  PubMed  CAS  Google Scholar 

  5. Ricciardolo, F.L., G.U. Di Maria, A. Mistretta, M.A. Sapienza, and P. Geppetti. 1997. Impairment of bronchoprotection by nitric oxide in severe asthma. Lancet 350: 1297–1298.

    Article  PubMed  CAS  Google Scholar 

  6. Guo, F.H., S.A. Comhair, S. Zheng, R.A. Dweik, N.T. Eissa, M.J. Thomassen, W. Calhoun, and S.C. Erzurum. 2000. Molecular mechanisms of increased nitric oxide (NO) in asthma: Evidence for transcriptional and post-translational regulation of NO synthesis. Journal of Immunology 164: 5970–5980.

    CAS  Google Scholar 

  7. de Boer, J., H. Meurs, W. Coers, M. Koopal, A.E. Bottone, A.C. Visser, W. Timens, and J. Zaagsma. 1996. Deficiency of nitric oxide in allergen-induced airway hyperreactivity to contractile agonists after the early asthmatic reaction: An ex vivo study. British Journal of Pharmacology 119: 1109–1116.

    Article  PubMed  Google Scholar 

  8. Maarsingh, H., J. Leusink, I.S. Bos, J. Zaagsma, and H. Meurs. 2006. Arginase strongly impairs neuronal nitric oxide-mediated airway smooth muscle relaxation in allergic asthma. Respiratory Research 7: 6.

    Article  PubMed  Google Scholar 

  9. Maarsingh, H., A.B. Zuidhof, I.S. Bos, M. van Duin, J.L. Boucher, J. Zaagsma, and H. Meurs. 2008. Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness, and inflammation. American Journal of Respiratory and Critical Care Medicine 178: 565–573.

    Article  PubMed  CAS  Google Scholar 

  10. North, M.L., N. Khanna, P.A. Marsden, H. Grasemann, and J.A. Scott. 2009. Functionally important role for arginase 1 in the airway hyperresponsiveness of asthma. American Journal of Physiology. Lung Cellular and Molecular Physiology 296: L911–L920.

    Article  PubMed  CAS  Google Scholar 

  11. Ricciardolo, F.L., M.C. Timmers, P. Geppetti, A. van Schadewijk, J.J. Brahim, J.K. Sont, H.W. de Gouw, P.S. Hiemstra, J.H. van Krieken, and P.J. Sterk. 2001. Allergen-induced impairment of bronchoprotective nitric oxide synthesis in asthma. Journal of Allergy and Clinical Immunology 108: 198–204.

    Article  PubMed  CAS  Google Scholar 

  12. Zimmermann, N., N.E. King, J. Laporte, M. Yang, A. Mishra, S.M. Pope, E.E. Muntel, D.P. Witte, A.A. Pegg, P.S. Foster, Q. Hamid, and M.E. Rothenberg. 2003. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. The Journal of Clinical Investigation 111: 1863–1874.

    PubMed  CAS  Google Scholar 

  13. Kharitonov, S.A., and P.J. Barnes. 2000. Clinical aspects of exhaled nitric oxide. European Respiratory Journal 16: 781–792.

    Article  PubMed  CAS  Google Scholar 

  14. Ckless, K., A. Lampert, J. Reiss, D. Kasahara, M.E. Poynter, C.G. Irvin, L.K. Lundblad, R. Norton, A. van der Vliet, and Y.M. Janssen-Heininger. 2008. Inhibition of arginase activity enhances inflammation in mice with allergic airway disease, in association with increases in protein S-nitrosylation and tyrosine nitration. Journal of Immunology 181: 4255–4264.

    CAS  Google Scholar 

  15. Takahashi, N., K. Ogino, K. Takemoto, S. Hamanishi, D.H. Wang, T. Takigawa, M. Shibamori, H. Ishiyama, and Y. Fujikura. 2010. Direct inhibition of arginase attenuated airway allergic reactions and inflammation in a Dermatophagoides farinae-induced NC/Nga mouse model. American Journal of Physiology. Lung Cellular and Molecular Physiology 299: L17–L24.

    Article  PubMed  CAS  Google Scholar 

  16. Ogino, K., Y. Obase, N. Takahashi, H. Shimizu, T. Takigawa, D.H. Wang, K. Ouchi, and M. Oka. 2010. High serum arginase I levels in asthma: Its correlation with high-sensitivity C-reactive protein. The Journal of Asthma 48: 1–7.

    Article  PubMed  Google Scholar 

  17. Lindemann, D., and K. Racke. 2003. Glucocorticoid inhibition of interleulin-4 (IL-4) and interleukin-13 (IL-13) induced up-regulation of arginase in rat airway fibroblasts. Naunyn-Schmiedeberg’s Archives of Pharmacology 368: 546–550.

    Article  PubMed  CAS  Google Scholar 

  18. Shibamori, M., K. Ogino, Y. Kambayashi, and H. Ishiyama. 2006. Intranasal mite allergen induces allergic asthma-like responses in NC/Nga mice. Life Sciences 78: 987–994.

    Article  PubMed  CAS  Google Scholar 

  19. Takemoto, K., K. Ogino, M. Shibamori, T. Gondo, Y. Hitomi, T. Takigawa, D.H. Wang, J. Takaki, H. Ichimura, Y. Fujikura, and H. Ishiyama. 2007. Transiently, paralleled upregulation of arginase and nitric oxide synthase and the effect of both enzymes on the pathology of asthma. American Journal of Physiology. Lung Cellular and Molecular Physiology 293: L1419–L1426.

    Article  PubMed  CAS  Google Scholar 

  20. Nagai, H., S. Yamaguchi, N. Inagaki, N. Tsuruoka, Y. Hitoshi, and K. Takatsu. 1993. Effect of anti-IL-5 monoclonal antibody on allergic bronchial eosinophilia and airway hyperresponsiveness in mice. Life Sciences 53: PL243–PL247.

    Article  PubMed  CAS  Google Scholar 

  21. Laemmli, U.K. 1970. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680–685.

    Article  PubMed  CAS  Google Scholar 

  22. Corraliza, I.M., M.L. Campo, G. Soler, and M. Modolell. 1994. Determination of arginase activity in macrophages: A micromethod. Journal of Immunological Methods 174: 231–235.

    Article  PubMed  CAS  Google Scholar 

  23. Yang, B.K., E.X. Vivas, C.D. Reiter, and M.T. Gladwin. 2003. Methodologies for the sensitive and specific measurement of S-nitrosothiols, iron-nitrosyls, and nitrite in biological samples. Free Radical Research 37: 1–10.

    Article  PubMed  CAS  Google Scholar 

  24. Lee, K.S., H.K. Lee, J.S. Hayflick, Y.C. Lee, and K.D. Puri. 2006. Inhibition of phosphoinositide 3-kinase attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model. The FASEB Journal 20: 455–465.

    Article  CAS  Google Scholar 

  25. Tournoy, K.G., J.C. Kips, C. Schou, and R.A. Pauwels. 2000. Airway eosinophilia is not a requirement for allergen-induced airway hyperresponsiveness. Clinical and Experimental Allergy 30: 79–85.

    Article  PubMed  CAS  Google Scholar 

  26. Barnes, P.J. 2010. Mechnaisms and resistance in glucocorticoid control of inflammation. The Journal of Steroid Biochemistry and Molecular Biology 120: 76–85.

    Article  PubMed  CAS  Google Scholar 

  27. Miloux, B., P. Laurent, O. Bonnin, J. Lupker, D. Caput, N. Vita, and P. Ferrara. 1997. Cloning of the human IL-13R alpha1 chain and reconstitution with the IL4R alpha of a functional IL-4/IL-13 receptor complex. FEBS Letters 401: 163–166.

    Article  PubMed  CAS  Google Scholar 

  28. Xie, Q.W., Y. Kashiwabara, and C. Nathan. 1994. Role of transcription factor NF-kappaB/Rel in induction of nitric oxide synthase. Journal of Biological Chemistry 269: 4705–4708.

    PubMed  CAS  Google Scholar 

  29. Marshall, H.E., and J.S. Stamler. 2001. Inhibition of NF-κB by S-nitrosylation. Biochemistry 40: 1688–1693.

    Article  PubMed  CAS  Google Scholar 

  30. Galigniana, M.D., G. Piwien-Pilipuk, and J. Assreuy. 1999. Inhibition of glucocorticoid receptor binding by nitric oxide. Molecular Pharmacology 55: 317–323.

    PubMed  CAS  Google Scholar 

  31. Bratt, J.M., L.M. Franzi, A.L. Linderholm, M.S. Last, N.J. Kenyon, and J.A. Last. 2009. Arginase enzymes in isolated airways from normal and nitric oxide synthase 2-knockout mice exposed to ovalbumin. Toxicology and Applied Pharmacology 234: 273–280.

    Article  PubMed  CAS  Google Scholar 

  32. Maarsingh, H., B.E. Bossenga, I.S. Bos, H.H. Volders, J. Zaagsma, and H. Meurs. 2009. L-arginine deficiency causes airway hyperresponsiveness after the late asthmatic reaction. European Respiratory Journal 34: 191–199.

    Article  PubMed  CAS  Google Scholar 

  33. Meurs, H., S. McKay, H. Maarsingh, M.A. Hamer, L. Macic, N. Molendijk, and J. Zaagsma. 2002. Increased arginase activity underlies allergen-induced deficiency of cNOS-derived nitric oxide and airway hyperresponsiveness. British Journal of Pharmacology 136: 391–398.

    Article  PubMed  CAS  Google Scholar 

  34. Obianyo, O., T.C. Osborne, and P.R. Thompson. 2008. Kinetic mechanism of protein arginine methyltransferase 1. Biochemistry 47: 10420–10427.

    Article  PubMed  CAS  Google Scholar 

  35. Wells, S.M., and A. Holian. 2007. Asymmetric dimethylarginine induces oxidative and nitrosative stress in murine lung epithelial cells. American Journal of Respiratory Cell and Molecular Biology 36: 520–528.

    Article  PubMed  CAS  Google Scholar 

  36. Ahmad, T., U. Mabalirajan, B. Ghosh, and A. Agrawal. 2010. Altered asymmetric dimethyl arginine metabolism in allergically inflamed mouse lungs. American Journal of Respiratory Cell and Molecular Biology 42: 3–8.

    Article  PubMed  CAS  Google Scholar 

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ACKNOWLEDGMENTS

This work was supported in part by Grant-in-Aid for Science Research (B) (23390163) from the Ministry of Education, Culture, Sports, Science, and Technology of the Japanese Government.

Conflict of Interest

No conflicts of interest, financial or otherwise, are declared by the author(s).

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Authors and Affiliations

  1. Department of Public Health, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Okayama, 700-8558, Japan

    Keiki Ogino, Masayuki Kubo, Hidekazu Takahashi, Ran Zhang & Yu Zou

  2. Division of Morphological Analysis, Department of Anatomy, Biology and Medicine, Faculty of Medicine, Oita University, 1-1, Idaigaoka, Hasama-machi, Yufu, Oita, Japan

    Yoshihisa Fujikura

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  1. Keiki Ogino
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  2. Masayuki Kubo
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Correspondence to Keiki Ogino.

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Ogino, K., Kubo, M., Takahashi, H. et al. Anti-inflammatory Effect of Arginase Inhibitor and Corticosteroid on Airway Allergic Reactions in a Dermatophogoides farinae-induced NC/Nga Mouse Model. Inflammation 36, 141–151 (2013). https://doi.org/10.1007/s10753-012-9529-3

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  • DOI: https://doi.org/10.1007/s10753-012-9529-3

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