Skip to main content

Advertisement

SpringerLink
Log in

Upregulation of ADAM8 in the Airways of Mice with Allergic Bronchial Asthma

  • Published:
Lung Aims and scope Submit manuscript

Abstract

Recent microarray analyses revealed that a disintegrin and metalloproteinase (ADAM) 8 (ADAM8; also called CD156) is one of the asthma candidate genes. However, the function of ADAM8 and its localization in the airways are still poorly understood. In the present study, the changes in the expression and localization of ADAM8 in the airways of a mouse model of allergic bronchial asthma were investigated. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen to induce asthmatic response. After the final antigen challenge, mRNA and protein expressions of ADAM8 were elucidated by quantitative RT-PCR and immunohistochemistry. The mRNA expression of ADAM8 in the airways was significantly increased in this animal model of asthma compared with naive animals. Immunohistochemical examinations revealed that ADAM8 was located in airway epithelia, airway smooth muscles, and infiltrated cells (mainly macrophages) into lung parenchyma. A distinctly stronger immunostaining of ADAM8 was observed in these airway cells of the repeatedly antigen-challenged mice compared with those of the sensitized control animals. An upregulation of ADAM8 in the airways might be involved in the pathogenesis of airway inflammation and/or hyperresponsiveness, characteristic features of allergic bronchial asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. Masoli M, Fabian D, Holt S, Beasley R (2004) Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy 59:469–478. doi:10.1111/j.1398-9995.2004.00526.x

    Article  PubMed  Google Scholar 

  2. National Asthma Education and Prevention Program Expert Panel Report 3 (EPR-3) (2007) Guidelines for the diagnosis and management of asthma-summary report 2007. J Allergy Clin Immunol 120:S94–S138. doi:10.1016/j.jaci.2007.09.029

    Article  Google Scholar 

  3. Zimmermann N, King NE, Laporte J, Yang M, Mishra A, Pope SM, Muntel EE, Witte DP, Pegg AA, Foster PS, Hamid Q, Rothenberg ME (2003) Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 111:1863–1874

    PubMed  CAS  Google Scholar 

  4. King NE, Zimmermann N, Pope SM, Fulkerson PC, Nikolaidis NM, Mishra A, Witte DP, Rothenberg ME (2004) Expression and regulation of a disintegrin and metalloproteinase (ADAM) 8 in experimental asthma. Am J Respir Cell Mol Biol 31:257–265. doi:10.1165/rcmb.2004-0026OC

    Article  PubMed  CAS  Google Scholar 

  5. Huovila AP, Turner AJ, Pelto-Huikko M, Kärkkäinen I, Ortiz RM (2005) Shedding light on ADAM metalloproteinases. Trends Biochem Sci 30:413–422. doi:10.1016/j.tibs.2005.05.006

    Article  PubMed  CAS  Google Scholar 

  6. Seals DF, Courtneidge SA (2003) The ADAMs family of metalloproteases: multidomain proteins with multiple functions. Genes Dev 17:7–30. doi:10.1101/gad.1039703

    Article  PubMed  CAS  Google Scholar 

  7. Fourie AM, Coles F, Moreno V, Karlsson L (2003) Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23. J Biol Chem 278:30469–30477. doi:10.1074/jbc.M213157200

    Article  PubMed  CAS  Google Scholar 

  8. Naus S, Reipschläger S, Wildeboer D, Lichtenthaler SF, Mitterreiter S, Guan Z, Moss ML, Bartsch JW (2006) Identification of candidate substrates for ectodomain shedding by the metalloprotease-disintegrin ADAM8. Biol Chem 387:337–346. doi:10.1515/BC.2006.045

    Article  PubMed  CAS  Google Scholar 

  9. Armant M, Ishihara H, Rubio M, Delespesse G, Sarfati M (1994) Regulation of cytokine production by soluble CD23: costimulation of interferon gamma secretion and triggering of tumor necrosis factor alpha release. J Exp Med 180:1005–1011. doi:10.1084/jem.180.3.1005

    Article  PubMed  CAS  Google Scholar 

  10. Armant M, Rubio M, Delespesse G, Sarfati M (1995) Soluble CD23 directly activates monocytes to contribute to the antigen-independent stimulation of resting T cells. J Immunol 155:4868–4875

    PubMed  CAS  Google Scholar 

  11. Bonnefoy JY, Plater-Zyberk C, Lecoanet-Henchoz S, Gauchat JF, Aubry JP, Graber P (1996) A new role for CD23 in inflammation. Immunol Today 17:418–420. doi:10.1016/0167-5699(96)10054-2

    Article  PubMed  CAS  Google Scholar 

  12. Paulissen G, Rocks N, Quesada-Calvo F, Gosset P, Foidart JM, Noel A, Louis R, Cataldo DD (2006) Expression of ADAMs and their inhibitors in sputum from patients with asthma. Mol Med 12:171–179. doi:10.2119/2006-00028

    Article  PubMed  CAS  Google Scholar 

  13. Foley SC, Mogas AK, Olivenstein R, Fiset PO, Chakir J, Bourbeau J, Ernst P, Lemière C, Martin JG, Hamid Q (2007) Increased expression of ADAM33 and ADAM8 with disease progression in asthma. J Allergy Clin Immunol 119:863–871. doi:10.1016/j.jaci.2006.12.665

    Article  PubMed  CAS  Google Scholar 

  14. Matsuno O, Kumamoto T, Higuchi Y (2008) ADAM8 in allergy. Inflamm Allergy Drug Targets 7:108–112. doi:10.2174/187152808785107598

    Article  PubMed  CAS  Google Scholar 

  15. Chiba Y, Ueno A, Sakai H, Misawa M (2004) Hyperresponsiveness of bronchial but not tracheal smooth muscle in a murine model of allergic bronchial asthma. Inflamm Res 53:636–642. doi:10.1007/s00011-004-1305-x

    Article  PubMed  CAS  Google Scholar 

  16. Chiba Y, Kurotani R, Kusakabe T, Miura T, Link BW, Misawa M, Kimura S (2006) Uteroglobin-related protein 1 expression suppresses allergic airway inflammation in mice. Am J Respir Crit Care Med 173:958–964. doi:10.1164/rccm.200503-456OC

    Article  PubMed  CAS  Google Scholar 

  17. Inoue K, Takano H, Yanagisawa R, Sakurai M, Ichinose T, Sadakane K, Yoshikawa T (2005) Effects of nano particles on antigen-related airway inflammation in mice. Respir Res 6:106. doi:10.1186/1465-9921-6-106

    Article  PubMed  Google Scholar 

  18. Yoshida S, Setoguchi M, Higuchi Y, Akizuki S, Yamamoto S (1990) Molecular cloning of cDNA encoding MS2 antigen, a novel cell surface antigen strongly expressed in murine monocytic lineage. Int Immunol 2:585–591. doi:10.1093/intimm/2.6.585

    Article  PubMed  CAS  Google Scholar 

  19. Yamamoto S, Higuchi Y, Yoshiyama K, Shimizu E, Kataoka M, Hijiya N, Matsuura K (1990) ADAM family proteins in the immune system. Immunol Today 20:278–284. doi:10.1016/S0167-5699(99)01464-4

    Article  Google Scholar 

  20. Yoshiyama K, Higuchi Y, Kataoka M, Matsuura K, Yamamoto S (1997) CD156 (human ADAM8): expression, primary amino acid sequence, and gene location. Genomics 41:56–62. doi:10.1006/geno.1997.4607

    Article  PubMed  CAS  Google Scholar 

  21. Kataoka M, Yoshiyama K, Matsuura K, Hijiya N, Higuchi Y, Yamamoto S (1997) Structure of the murine CD156 gene, characterization of its promoter, and chromosomal location. J Biol Chem 272:18209–18215. doi:10.1074/jbc.272.29.18209

    Article  PubMed  CAS  Google Scholar 

  22. Higuchi Y, Yasui A, Matsuura K, Yamamoto S (2002) CD156 transgenic mice different responses between inflammatory types. Pathobiology 70:47–54. doi:10.1159/000066003

    Article  PubMed  CAS  Google Scholar 

  23. Smalley DM, Ley K (2005) L-Selectin: mechanisms and physiological significance of ectodomain cleavage. J Cell Mol Med 9:255–266. doi:10.1111/j.1582-4934.2005.tb00354.x

    Article  PubMed  CAS  Google Scholar 

  24. Gómez-Gaviro M, Domínguez-Luis M, Canchado J, Calafat J, Janssen H, Lara-Pezzi E, Fourie A, Tugores A, Valenzuela-Fernández A, Mollinedo F, Sánchez-Madrid F, Díaz-González F (2007) Expression and regulation of the metalloproteinase ADAM-8 during human neutrophil pathophysiological activation and its catalytic activity on L-selectin shedding. J Immunol 178:8053–8063

    PubMed  Google Scholar 

  25. Chiba Y, Nakazawa S, Todoroki M, Shinozaki K, Sakai H, Misawa M (2009) Interleukin-13 augments bronchial smooth muscle contractility with an up-regulation of RhoA protein. Am J Respir Cell Mol Biol 40:159–167. doi:10.1165/rcmb.2008-0162OC

    Article  PubMed  CAS  Google Scholar 

  26. Matsuno O, Miyazaki E, Nureki S, Ueno T, Ando M, Ito K, Kumamoto T, Higuchi Y (2007) Elevated soluble ADAM8 in bronchoalveolar lavage fluid in patients with eosinophilic pneumonia. Int Arch Allergy Immunol 142:285–290. doi:10.1159/000097359

    Article  PubMed  CAS  Google Scholar 

  27. Dasic G, Juillard P, Graber P, Herren S, Angell T, Knowles R, Bonnefoy JY, Kosco-Vilbois MH, Chvatchko Y (1999) Critical role of CD23 in allergen-induced bronchoconstriction in a murine model of allergic asthma. Eur J Immunol 29:2957–2967. doi:10.1002/(SICI)1521-4141(199909)29:09<2957::AID-IMMU2957>3.0.CO;2-4

    Article  PubMed  CAS  Google Scholar 

  28. Haczku A, Takeda K, Hamelmann E, Loader J, Joetham A, Redai I, Irvin CG, Lee JJ, Kikutani H, Conrad D, Gelfand EW (2000) CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness. Am J Respir Crit Care Med 161:952–960

    PubMed  CAS  Google Scholar 

  29. Cernadas M, De Sanctis GT, Krinzman SJ, Mark DA, Donovan CE, Listman JA, Kobzik L, Kikutani H, Christiani DC, Perkins DL, Finn PW (1999) CD23 and allergic pulmonary inflammation: potential role as an inhibitor. Am J Respir Cell Mol Biol 20:1–8

    PubMed  CAS  Google Scholar 

  30. McCloskey N, Hunt J, Beavil RL, Jutton MR, Grundy GJ, Girardi E, Fabiane SM, Fear DJ, Conrad DH, Sutton BJ, Gould HJ (2007) Soluble CD23 monomers inhibit and oligomers stimulate IGE synthesis in human B cells. J Biol Chem 282:24083–24091. doi:10.1074/jbc.M703195200

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Sachiko Ito, Yuichi Nishida, and Kumiko Goto for their help with technical assistance.

Author information

Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Yoshihiko Chiba, Satoshi Onoda, Hiroyasu Sakai & Miwa Misawa

  2. Fine Drug Targeting Research Laboratory, Institute of Medicinal Chemistry, School of Pharmacy, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo, 142-8501, Japan

    Yoshiyuki Hattori & Yoshie Maitani

Authors
  1. Yoshihiko Chiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satoshi Onoda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshiyuki Hattori
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshie Maitani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hiroyasu Sakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Miwa Misawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshihiko Chiba.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chiba, Y., Onoda, S., Hattori, Y. et al. Upregulation of ADAM8 in the Airways of Mice with Allergic Bronchial Asthma. Lung 187, 179–185 (2009). https://doi.org/10.1007/s00408-009-9145-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-009-9145-7

Keywords

Search

Navigation