PARP-1 Inhibition Provides Protection Against Elastase-induced Emphysema by Mitigating the Expression of Matrix Metalloproteinases

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 2019 Apr 18

PMID 30993494

Citations 9

Authors

Vivek Dharwal

Rajat Sandhir

Amarjit S Naura

Affiliations

Soon will be listed here.

Abstract

In our previous study, we have shown that PARP-1 inhibition (genetic or pharmacological) ameliorates elastase-induced inflammation and emphysema. Since matrix metalloproteinases (MMPs) particularly MMP-2 and MMP-9 are known to play a critical role in emphysema development, the present work was designed to evaluate the effects of PARP-1 inhibition on their expression utilizing elastase-induced mouse model of emphysema. Our data show that olaparib administration at a dose of 5 mg/kg b.wt. (daily) significantly prevented the elastase-induced inflammation as indicated by decreased inflammatory cells particularly macrophages in BALF at 1 week post-injury. In addition, the drug restored the altered redox balance in the lungs of elastase-treated mice toward normal. Further, PCR data show that olaparib administration ameliorates the elastase-induced expression of MMP-2 and MMP-9 without having much effect on the expressions of their inhibitors TIMP-1 and TIMP-2. Next, our data on immunoblot, gelatin zymography, and immunohistochemical analysis indeed confirm that olaparib reduced the elastase-induced expression of MMP-2 and MMP-9. Reduction in the expression of metalloproteinases correlate well with the PARP activity as olaparib treatment suppressed the elastase-induced expression of PAR modified proteins markedly. Overall, our data strongly suggest that PARP-1 inhibition blunts elastase-induced MMP-2 and MMP-9 expression, which may be partly responsible for prevention of emphysema.

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References

Pardo A, Gaxiola M, Uhal B, Becerril C, Selman M . Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest. 2000; 117(3):684-94. DOI: 10.1378/chest.117.3.684. View

English W, Puente X, Freije J, Knauper V, Amour A, Merryweather A . Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-alpha convertase activity but does not activate pro-MMP2. J Biol Chem. 2000; 275(19):14046-55. DOI: 10.1074/jbc.275.19.14046. View

Tetley T . Macrophages and the pathogenesis of COPD. Chest. 2002; 121(5 Suppl):156S-159S. DOI: 10.1378/chest.121.5_suppl.156s. View

Mohan M, Seaton T, Mitchell J, Howe A, Blackburn K, Burkhart W . The tumor necrosis factor-alpha converting enzyme (TACE): a unique metalloproteinase with highly defined substrate selectivity. Biochemistry. 2002; 41(30):9462-9. DOI: 10.1021/bi0260132. View

LOWRY O, ROSEBROUGH N, FARR A, RANDALL R . Protein measurement with the Folin phenol reagent. J Biol Chem. 1951; 193(1):265-75. View

Corry D, Kiss A, Song L, Song L, Xu J, Lee S . Overlapping and independent contributions of MMP2 and MMP9 to lung allergic inflammatory cell egression through decreased CC chemokines. FASEB J. 2004; 18(9):995-7. PMC: 2771179. DOI: 10.1096/fj.03-1412fje. View

Vernooy J, Lindeman J, Jacobs J, Hanemaaijer R, Wouters E . Increased activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in induced sputum from patients with COPD. Chest. 2004; 126(6):1802-10. DOI: 10.1378/chest.126.6.1802. View

Barnes P . Mediators of chronic obstructive pulmonary disease. Pharmacol Rev. 2004; 56(4):515-48. DOI: 10.1124/pr.56.4.2. View

Lagente V, Manoury B, Nenan S, Le Quement C, Martin-Chouly C, Boichot E . Role of matrix metalloproteinases in the development of airway inflammation and remodeling. Braz J Med Biol Res. 2005; 38(10):1521-30. DOI: 10.1590/s0100-879x2005001000009. View

10.

MacNee W . Pathogenesis of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005; 2(4):258-66. PMC: 2713323. DOI: 10.1513/pats.200504-045SR. View

11.

Castaneda F, Walia B, Vijay-Kumar M, Patel N, Roser S, Kolachala V . Targeted deletion of metalloproteinase 9 attenuates experimental colitis in mice: central role of epithelial-derived MMP. Gastroenterology. 2005; 129(6):1991-2008. DOI: 10.1053/j.gastro.2005.09.017. View

12.

Barnes P . Transcription factors in airway diseases. Lab Invest. 2006; 86(9):867-72. DOI: 10.1038/labinvest.3700456. View

13.

Barnes P . Alveolar macrophages as orchestrators of COPD. COPD. 2006; 1(1):59-70. DOI: 10.1081/COPD-120028701. View

14.

Rhee J, Lee K, Kim D, Lee Y, Jeon O, Kwon H . NF-kappaB-dependent regulation of matrix metalloproteinase-9 gene expression by lipopolysaccharide in a macrophage cell line RAW 264.7. J Biochem Mol Biol. 2007; 40(1):88-94. DOI: 10.5483/bmbrep.2007.40.1.088. View

15.

Churg A, Wang R, Wang X, Onnervik P, Thim K, Wright J . Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs. Thorax. 2007; 62(8):706-13. PMC: 2117295. DOI: 10.1136/thx.2006.068353. View

16.

Baraldo S, Bazzan E, Zanin M, Turato G, Garbisa S, Maestrelli P . Matrix metalloproteinase-2 protein in lung periphery is related to COPD progression. Chest. 2007; 132(6):1733-40. DOI: 10.1378/chest.06-2819. View

17.

Manicone A, McGuire J . Matrix metalloproteinases as modulators of inflammation. Semin Cell Dev Biol. 2007; 19(1):34-41. PMC: 2235912. DOI: 10.1016/j.semcdb.2007.07.003. View

18.

Adair-Kirk T, Senior R . Fragments of extracellular matrix as mediators of inflammation. Int J Biochem Cell Biol. 2008; 40(6-7):1101-10. PMC: 2478752. DOI: 10.1016/j.biocel.2007.12.005. View

19.

Lan Y, Zhang C, Xiao J, Zhuo Y, Guo H, Peng W . Suppression of IkappaBalpha increases the expression of matrix metalloproteinase-2 in human ciliary muscle cells. Mol Vis. 2009; 15:1977-87. PMC: 2756517. View

20.

Hans C, Feng Y, Naura A, Troxclair D, Zerfaoui M, Siddiqui D . Opposing roles of PARP-1 in MMP-9 and TIMP-2 expression and mast cell degranulation in dyslipidemic dilated cardiomyopathy. Cardiovasc Pathol. 2010; 20(2):e57-68. PMC: 3159956. DOI: 10.1016/j.carpath.2010.03.007. View