Mechanisms of allergyProteinase-activated receptor-2–mediated matrix metalloproteinase-9 release from airway epithelial cells☆,☆☆,★
Section snippets
Material
Pancreatic trypsin, dexamethasone, and MG-132 (Cbz-Leu-Leu-leucinal; Sigma-Aldrich Canada LTD, Oakville, Ontario, Canada); recombinant human TNF (Cedarlane Laboratories Ltd, Ontario, Canada); Trizol, murine Moloney leukemia virus reverse transcriptase, Taq polymerase, oligo-dT primers, (Gibco BRL, Ontario, Canada); Fura-2 (Molecular Probes Inc, Eugene, Ore); Dulbecco’s modified Eagle’s medium (DMEM), FCS, penicillin, streptomycin, and L -glutamine (Biowhittaker, Walkersville, Md) were purchased
PAR-2 activation induces MMP-9 mRNA and enzymatic activity in A549 cells
Trypsin (10 U/mL) induced a sharp increase in the intracellular Ca++ concentration in A549 cells (Fig l), as did the PAR-2–activating peptide tc-LIGRLO-NH2 (70 μmmol/L; Fig 1). The inactive peptide LRGILS-NH2 had no effect. Although treatment of the cells with trypsin desensitized the PAR-2 response to tc-LIGRLO-NH2 (Fig 1), pretreatment of the cells with
Discussion
In this study, we demonstrated that PAR-2–mediated activation of airway epithelial cells upregulated the synthesis and release of pro–MMP-9. MMP-9 was secreted in the proenzyme form from epithelial cells after PAR-2 activation. Recently, PAR-2 activation has been shown to cause relaxation of airways that was mediated by the release of cyclooxygenase products from airway epithelium,24 which indicates a protective role for airway epithelial cell PAR-2. Our results indicate that the effect of
Acknowledgements
The authors thank Ms Jolanda Sawicka and Dr Greg Sawicki for providing positive controls for MMP-2 and MMP-9 gelatin zymography and TIMP-1 and TIMP-2 Western blot analysis.
References (52)
- et al.
Induction of macrophage metalloproteinases by extracellular matrix: evidence for enzyme- and substrate-specific responses involving prostaglandin-dependent mechanisms
J Biol Chem
(1993) - et al.
Structure and expression of neutrophil gelatinase cDNA: identity with type IV collagenase from HT1080 cells
J Biol Chem
(1992) - et al.
Structural biochemistry and activation of matrix metalloproteases
Curr Opin Cell Biol
(1993) - et al.
Expression of matrix metalloproteinase gelatinases A and B by cultured epithelial cells from human bronchial explants
J Biol Chem
(1996) - et al.
The proteinase-activated receptor 2 is induced by inflammatory mediators in human endothelial cells: comparison with the thrombin receptor
J Biol Chem
(1996) - et al.
A new generation of Ca2+ indicators with greatly improved fluorescence properties
J Biol Chem
(1985) - et al.
Regulation of expression of matrix metalloproteinase-9 in early human T cells of the HSB.2 cultured line by the EP3 subtype of prostaglandin E2 receptor
J Biol Chem
(1996) - et al.
The MKK6/p38 stress kinase cascade is critical for tumor necrosis factor-alpha–induced expression of monocyte-chemoattractant protein-1 in endothelial cells
Blood
(1999) - et al.
Expression of trypsin by epithelial cells of various tissues, leukocytes, and neurons in human and mouse
Am J Pathol
(1998) Tryptase, a mediator of human mast cells
J Allergy Clin Immunol
(1990)
Efficacy of inhaled corticosteroids in asthma
J Allergy Clin Immunol
Remodeling of asthmatic airways by glucocorticosteroids
J Allergy Clin Immunol
Direct inhibition of cyclooxygenase-1 and -2 by the kinase inhibitors SB 203580 and PD 98059: SB 203580 also inhibits thromboxane synthase
J Biol Chem
Eosino-phils as a source of matrix metalloproteinase-9 in asthmatic airway inflammation
Am J Respir Cell Mol Biol
Mast cell expression of gelatinases A and B is regulated by kit ligand and TGF-beta
J Immunol
Inhibition of matrix metalloproteinases prevents allergen-induced airway inflammation in a murine model of asthma
J Immunol
Regulatory effects of endogenous protease inhibitors in acute lung inflammatory injury
J Immunol
Increased release of matrix metalloproteinase-9 in bronchoalveolar lavage fluid and by alveolar macrophages of asthmatics
Am J Respir Cell Mol Biol
Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation during status asthmaticus
Am J Respir Crit Care Med
Sputum metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio correlates with airflow obstruction in asthma and chronic bronchitis
Am J Respir Crit Care Med
Migration of eosinophils through basement membrane components in vitro: role of matrix metalloproteinase-9
Am J Respir Cell Mol Biol
T cell gelatinases mediate basement membrane transmigration in vitro
J Immunol
Cell-matrix interactions modulate 92-kD gelatinase expression by human bronchial epithelial cells
Am J Respir Cell Mol Biol
Proteinase-activated receptors: novel mechanisms of signaling by serine proteases
Am J Physiol
Mast cell tryptase regulates rat colonic myocytes through proteinase-activated receptor 2
J Clin Invest
Increased vascular permeability by a specific agonist of protease-activated receptor-2 in rat hindpaw
Br J Pharmacol
Cited by (159)
Collagenolytic matrix metalloproteinases antagonize proteinase-activated receptor-2 activation, providing insights into extracellular matrix turnover
2019, Journal of Biological ChemistryCitation Excerpt :To our knowledge, the expression of MMP-1 and MMP-13 in chondrocytes following PAR2 activation is a novel observation, although the addition of SLIGKV-NH2 to OA cartilage has previously been shown to increase MMP-1 and MMP-13 immunostaining (22). Aside from the collagenases, other MMPs, including MMP-2 (42), MMP-3 (43), and MMP-9 (44), have been shown to be induced by PAR2 activation in various cell types. Biased agonism following activator peptide stimulation of PAR2 has previously been explored.
Insulin decreases expression of the proinflammatory receptor proteinase-activated receptor-2 on human airway epithelial cells
2018, Journal of Allergy and Clinical ImmunologyHuman eosinophils constitutively express a unique serine protease, PRSS33
2017, Allergology InternationalThe effect of ozone on the expression of metallothionein in tissues of rats chronically exposed to cadmium
2017, Environmental Toxicology and PharmacologyMolecularly targeted therapies for asthma: Current development, challenges and potential clinical translation
2016, Pulmonary Pharmacology and Therapeutics
- ☆
Supported by an MRC/PMAC Fellowship, MRC Canada, Alberta Heritage Foundation of Medical Research (AHFMR) and Glaxo-Heritage.
- ☆☆
H.V. is an MRC Scholar and an Alberta Heritage Clinical Investigator. M.D. and R.M. are Alberta Heritage Senior Medical Scholars. A.D.B. holds the Astra Chair in Asthma Research. J.L.W. is an Alberta Heritage Scientist MRC and a Senior Scientist.
- ★
Reprint requests: Redwan Moqbel, PhD, FRCPath, Pulmonary Research Group, Department of Medicine 574 HMRC, University of Alberta, Edmonton, AB, T6G 2S2, Canada.