Skip to main content

Advertisement

Log in

Effect of a matrix metalloproteinase-12 inhibitor, S-1, on allergic airway disease phenotypes in mice

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

Matrix metalloproteinase-12 (MMP-12) has been reported to play an important role in chronic airway inflammatory diseases, but its detailed role in allergic airway disease is not well known. In this study, we investigated the expressions of MMP-12 and the effect of S-1, an MMP-12 inhibitor, in a mouse model of allergic airway inflammation.

Materials and methods

The expressions and activity of MMP-12 were measured by RT-PCR western blot and zymography, respectively. The locations in the airways of MMP-12 and elastin fiber were histologically studied. The mice were orally administered with S-1 during the period of antigen challenge. Bronchoalveolar lavage fluid (BALF) cells were counted, and the activity of MMP-12 in BALF was measured by zymography after the treatment with S-1.

Results

The allergen challenge model resulted in increased eosinophil number in BALF and damage to elastin fiber. Upregulation of MMP-12 was also found in the airways of challenged mice. The increased eosinophil number in the BALF after antigen challenge was inhibited by S-1.

Conclusion

These findings suggest that MMP-12 may play an important role in the eosinophil infiltration of the allergic airway.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. McCawley LJ, Matrisian LM. Matrix metalloproteinases: they’re not just for matrix anymore!. Curr Opin Cell Biol. 2001;13:534–40.

    Article  CAS  PubMed  Google Scholar 

  2. Starcher BC. Elastin and the lung. Thorax. 1986;41:577–85.

    Article  CAS  PubMed  Google Scholar 

  3. Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997;277:2002–4.

    Article  CAS  PubMed  Google Scholar 

  4. Demedts IK, Morel-Montero A, Lebecque S, Pacheco Y, Cataldo D, Joos GF, et al. Elevated MMP-12 protein levels in induced sputum from patients with COPD. Thorax. 2006;61:196–201.

    Article  CAS  PubMed  Google Scholar 

  5. Xie S, Issa R, Sukkar MB, Oltmanns U, Bhavsar PK, Papi A, et al. Induction and regulation of matrix metalloproteinase-12 in human airway smooth muscle cells. Respir Res. 2005;6:148.

    Article  PubMed  CAS  Google Scholar 

  6. Nénan S, Boichot E, Lagente V, Bertrand CP. Macrophage elastase (MMP-12): a pro-inflammatory mediator? Mem Inst Oswaldo Cruz. 2005; Suppl 1:167–72.

    Google Scholar 

  7. Warner RL, Lukacs NW, Shapiro SD, Bhagarvathula N, Nerusu KC, Varani J, et al. Role of metalloelastase in a model of allergic lung responses induced by cockroach allergen. Am J Pathol. 2004;165:1921–30.

    CAS  PubMed  Google Scholar 

  8. Lanone S, Zheng T, Zhu Z, Liu W, Lee CG, Ma B, et al. Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling. J Clin Invest. 2002;110:463–74.

    CAS  PubMed  Google Scholar 

  9. Chiba Y, Yu Y, Sakai H, Misawa M. Increase in the expression of matrix metalloproteinase-12 in the airways of rats with allergic bronchial asthma. Biol Pharm Bull. 2007;30:318–23.

    Article  CAS  PubMed  Google Scholar 

  10. Ko FW, Diba C, Roth M, McKay K, Johnson PR, Salome C, et al. A comparison of airway and serum matrix metalloproteinase-9 activity among normal subjects, asthmatic patients, and patients with asthmatic mucus hypersecretion. Chest. 2005;127:1919–27.

    Article  CAS  PubMed  Google Scholar 

  11. Corry DB, Kiss A, Song LZ, Song L, Xu J, Lee SH, et al. Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J. 2004;18:995–7.

    CAS  PubMed  Google Scholar 

  12. Kumagai K, Ohno I, Okada S, Ohkawara Y, Suzuki K, Shinya T, et al. Inhibition of matrix metalloproteinases prevents allergen-induced airway inflammation in a murine model of asthma. J Immunol. 1999;162:4212–9.

    CAS  PubMed  Google Scholar 

  13. Maekawa R, Maki H, Wada T, Yoshida H, Nishida-Nishimoto K, Okamoto H, et al. Anti-metastatic efficacy and safety of MMI-166, a selective matrix metalloproteinase inhibitor. Clin Exp Metastasis. 2000;18:61–6.

    Article  CAS  PubMed  Google Scholar 

  14. Tamura Y, Watanabe F, Nakatani T, Yasui K, Fuji M, Komurasaki T, et al. Highly selective and orally active inhibitors of type IV collagenase (MMP-9 and MMP-2): N-sulfonylamino acid derivatives. J Med Chem. 1998;41:640–9.

    Article  CAS  PubMed  Google Scholar 

  15. Curci JA, Liao S, Huffman MD, Shapiro SD, Thompson RW. Expression and localization of macrophage elastase (matrix metalloproteinase-12) in abdominal aortic aneurysms. J Clin Invest. 1998;102:1900–10.

    Article  CAS  PubMed  Google Scholar 

  16. Chiba Y, Kurotani R, Kusakabe T, Miura T, Link BW, Misawa M, et al. Uteroglobin-related protein 1 expression suppresses allergic airway inflammation in mice. Am J Respir Crit Care Med. 2006;173:958–64.

    Article  CAS  PubMed  Google Scholar 

  17. Inoue K, Takano H, Yanagisawa R, Sakurai M, Ichinose T, Sadakane K, et al. Effects of nano particles on antigen-related airway inflammation in mice. Respir Res. 2005;6:106.

    Article  PubMed  CAS  Google Scholar 

  18. Zhang RB, He QY, Yang RH, Lu BB, Liu YJ. Study on matrix metalloproteinase 1, 9, 12 polymorphisms and susceptibility to chronic obstructive pulmonary disease among Han nationality in northern China. Zhonghua Liu Xing Bing Xue Za Zhi. 2005;26:907–10.

    CAS  PubMed  Google Scholar 

  19. Wang X, Inoue S, Gu J, Miyoshi E, Noda K, Li W, et al. Dysregulation of TGF-beta1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice. Proc Natl Acad Sci USA. 2005;102:15791–6.

    Article  CAS  PubMed  Google Scholar 

  20. Kato Y, Manabe T, Tanaka Y, Mochizuki H. Effect of an orally active Th1/Th2 balance modulator, M50367, on IgE production, eosinophilia, and airway hyperresponsiveness in mice. J Immunol. 1999;162:7470–9.

    CAS  PubMed  Google Scholar 

  21. Shapiro SD, Kobayashi DK, Ley TJ. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem. 1993;268:23824–9.

    CAS  PubMed  Google Scholar 

  22. Pouladi MA, Robbins CS, Swirski FK, Cundall M, McKenzie AN, Jordana M, et al. Interleukin-13-dependent expression of matrix metalloproteinase-12 is required for the development of airway eosinophilia in mice. Am J Respir Cell Mol Biol. 2004;30:84–90.

    Article  CAS  PubMed  Google Scholar 

  23. Lavigne MC, Thakker P, Gunn J, Wong A, Miyashiro JS, Wasserman AM, et al. Human bronchial epithelial cells express and secrete MMP-12. Biochem Biophys Res Commun. 2004;2:534–46.

    Article  CAS  Google Scholar 

  24. Feinberg MW, Jain MK, Werner F, Sibinga NE, Wiesel P, Wang H, et al. Transforming growth factor-beta 1 inhibits cytokine-mediated induction of human metalloelastase in macrophages. J Biol Chem. 2000;275:25766–73.

    Article  CAS  PubMed  Google Scholar 

  25. Kips JC, Pauwels RA. Are cytokines responsible for the asthmatic state of the airways? Monaldi Arch Chest Dis. 1996;51:223–7.

    CAS  PubMed  Google Scholar 

  26. Uller L, Persson CG, Erjefält JS. Resolution of airway disease: removal of inflammatory cells through apoptosis, egression or both? Trends Pharmacol Sci. 2006;27:461–6.

    Article  CAS  PubMed  Google Scholar 

  27. Suzuki R, Miyazaki Y, Takagi K, Torii K, Taniguchi H. Matrix metalloproteinases in the pathogenesis of asthma and COPD: implications for therapy. Treat Respir Med. 2004;3:17–27.

    Article  CAS  PubMed  Google Scholar 

  28. Nénan S, Planquois JM, Hitier S, Berna P, Boichot E, Lagente V, et al. Modulation of MMP-12-induced pulmonary inflammation in mice by rolipram, dexamethasone and marimastat. Fundam Clin Pharmacol. 2004;18:S109.

    Google Scholar 

  29. Vaalamo M, Kariniemi AL, Shapiro SD, Saarialho-Kere U. Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration. J Invest Dermatol. 1999;112:499–505.

    Article  CAS  PubMed  Google Scholar 

  30. Cundall M, Sun Y, Miranda C, Trudeau JB, Barnes S, Wenzel SE. Neutrophil-derived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids. J Allergy Clin Immunol. 2003;112:1064–71.

    Article  CAS  PubMed  Google Scholar 

  31. DiScipio RG, Schraufstatter IU. The role of the complement anaphylatoxins in the recruitment of eosinophils. Int Immunopharmacol. 2007;7:1909–23.

    Article  CAS  PubMed  Google Scholar 

  32. Pégorier S, Wagner LA, Gleich GJ, Pretolani M. Eosinophil-derived cationic proteins activate the synthesis of remodeling factors by airway epithelial cells. J Immunol. 2006;177:4861–9.

    PubMed  Google Scholar 

  33. Lantz MS, Ciborowski P. Zymographic techniques for detection and characterization of microbial proteases. Methods Enzymol. 1994;235:563–94.

    Article  CAS  PubMed  Google Scholar 

  34. Gottlieb DJ, Stone PJ, Sparrow D, Gale ME, Weiss ST, Snider GL, et al. Urinary desmosine excretion in smokers with and without rapid decline of lung function: the Normative Aging Study. Am J Respir Crit Care Med. 1996;154:1290–5.

    CAS  PubMed  Google Scholar 

  35. Rosenbloom J, Abrams WR, Mecham R. Extracellular matrix 4: the elastic fiber. FASEB J. 1993;7:1208–18.

    CAS  PubMed  Google Scholar 

  36. Pham DN, Chu HW, Martin RJ, Kraft M. Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma. Ann Allergy Asthma Immunol. 2003;90:72–8.

    Article  CAS  PubMed  Google Scholar 

  37. Xisto DG, Farias LL, Ferreira HC, Picanço MR, Amitrano D, Lapa E, et al. Lung parenchyma remodeling in a murine model of chronic allergic inflammation. Am J Respir Crit Care Med. 2005;71:829–37.

    Article  Google Scholar 

  38. Mann BS, Chung KF. Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy. Respir Res. 2006;7:59.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yoshihiko Chiba.

Additional information

Responsible Editor: J. Skotnicki.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yu, Y., Chiba, Y., Sakai, H. et al. Effect of a matrix metalloproteinase-12 inhibitor, S-1, on allergic airway disease phenotypes in mice. Inflamm. Res. 59, 419–428 (2010). https://doi.org/10.1007/s00011-009-0153-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-009-0153-0

Keywords

Navigation