Effect of a matrix metalloproteinase-12 inhibitor, S-1, on allergic airway disease phenotypes in mice
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
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.
These findings suggest that MMP-12 may play an important role in the eosinophil infiltration of the allergic airway.
- McCawley LJ, Matrisian LM. Matrix metalloproteinases: they’re not just for matrix anymore!. Curr Opin Cell Biol. 2001;13:534–40. CrossRef
- Starcher BC. Elastin and the lung. Thorax. 1986;41:577–85. CrossRef
- Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Requirement for macrophage elastase for cigarette smoke-induced emphysema in mice. Science. 1997;277:2002–4. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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.
- 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.
- 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.
- 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. CrossRef
- 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. CrossRef
- 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.
- 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.
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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.
- 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. CrossRef
- 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.
- 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.
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- Kips JC, Pauwels RA. Are cytokines responsible for the asthmatic state of the airways? Monaldi Arch Chest Dis. 1996;51:223–7.
- 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. CrossRef
- 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. CrossRef
- 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.
- 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. CrossRef
- 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. CrossRef
- DiScipio RG, Schraufstatter IU. The role of the complement anaphylatoxins in the recruitment of eosinophils. Int Immunopharmacol. 2007;7:1909–23. CrossRef
- 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.
- Lantz MS, Ciborowski P. Zymographic techniques for detection and characterization of microbial proteases. Methods Enzymol. 1994;235:563–94. CrossRef
- 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.
- Rosenbloom J, Abrams WR, Mecham R. Extracellular matrix 4: the elastic fiber. FASEB J. 1993;7:1208–18.
- 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. CrossRef
- 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. CrossRef
- Mann BS, Chung KF. Blood neutrophil activation markers in severe asthma: lack of inhibition by prednisolone therapy. Respir Res. 2006;7:59. CrossRef
- Effect of a matrix metalloproteinase-12 inhibitor, S-1, on allergic airway disease phenotypes in mice
Volume 59, Issue 6 , pp 419-428
- Cover Date
- Print ISSN
- Online ISSN
- SP Birkhäuser Verlag Basel
- Additional Links
- Matrix metalloproteinase-12 (MMP-12)
- Airway inflammation
- Allergic airway disease
- Industry Sectors