Dissociation between the Effects of Oxygen and Pressure on Matrix Metalloproteinase-2, -7, and -9 Expression in Human Airway Epithelial Cells

ABSTRACT

We tested the hypothesis that hyperoxia or pressure exposure differentially activates expression of cytokines and/or matrix modeling proteins in human airway epithelial cells. Calu-3 epithelial cell monolayers were cultured on transwell plates with the apical surface exposed to gas. Following establishment of baseline, plates were placed in a chamber and exposed to: control (21% O₂; atm), hyperoxia (60% O₂; atm), pressure (21% O₂; 40 cm H₂O), and combination (60% O₂; 40 cm H₂O). At 72 hour of exposure, monolayers were assessed for integrity, viability, and expression of interleukin (IL)-6, IL-8 and matrix metalloproteinases (MMPs) -2, -7, and -9. Compared with controls, hyperoxia had lower transepithelial resistance (p < 0.001) and greater IL-6 secretion (p < 0.01), and pressure had lower cell viability (p < 0.001) and greater IL-8 secretion (p < 0.001). Hyperoxia resulted in more latent MMP-2 (p < 0.05) and MMP-7 (p < 0.001). Pressure was associated with a rise in MMPs independent of oxygen exposure (p < 0.05). Hyperoxia and pressure differentially affected MMP activities in Calu-3 cells and may lead to the different functional and structural abnormalities observed in these in vitro studies.

KEYWORDS

Conducting airway - mechanical ventilation - matrix modeling - inflammation - Calu-3

REFERENCES

• 1 Deoras K S, Wolfson M R, Searls R L, Hilfer S R, Shaffer T H. Developmental changes in tracheal structure.  Pediatr Res. 1991;  30 170-175
• 2 Panitch H B, Deoras K S, Wolfson M R, Shaffer T H. Maturational changes in airway smooth muscle structure-function relationships.  Pediatr Res. 1992;  31 151-156
• 3 Shaffer T H, Bhutani V K. Alterations in bulk modulus of tracheae during development.  Respiration. 1980;  39 344-350
• 4 Greenspan J S, Shaffer T H, Fox W W, Spitzer A R. Assisted ventilation: physiologic implications and complications. In: Polin RA, Fox WW, Abman SH Fetal and Neonatal Physiology. 3rd ed. Volume 1. Philadelphia; Saunders 2004: 961-978
• 5 Nagase H, Woessner Jr J F. Matrix metalloproteinases.  J Biol Chem. 1999;  274 21491-21494
• 6 Miller T L, Touch S M, Singhaus C J, Ramesh Babu P B, Chidekel A, Shaffer T H. Expression of matrix metalloproteinases 2, 7 and 9, and their tissue inhibitors 1 and 2, in developing rabbit tracheae.  Biol Neonate. 2005;  89 236-243
• 7 Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.  Circ Res. 2003;  92 827-839
• 8 Parks W C, Shapiro S D. Matrix metalloproteinases in lung biology.  Respir Res. 2001;  2 10-19
• 9 Miller T L, Shashikant B N, Pilon A L, Pierce R A, Shaffer T H, Wolfson M R. Effects of an intratracheally delivered anti-inflammatory protein (rhCC10) on physiological and lung structural indices in a juvenile model of acute lung injury.  Biol Neonate. 2005;  89 159-170
• 10 Infeld M D. Cell-matrix interactions in gland development in the lung.  Exp Lung Res. 1997;  23 161-169
• 11 Kheradmand F, Rishi K, Werb Z. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2.  J Cell Sci. 2002;  115(Pt 4) 839-848
• 12 Ganser G L, Stricklin G P, Matrisian L M. EGF and TGF alpha influence in vitro lung development by the induction of matrix-degrading metalloproteinases.  Int J Dev Biol. 1991;  35 453-461
• 13 Dunsmore S E, Saarialho-Kere U K, Roby J D et al.. Matrilysin expression and function in airway epithelium.  J Clin Invest. 1998;  102 1321-1331
• 14 Li Q, Park P W, Wilson C L, Parks W C. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury.  Cell. 2002;  111 635-646
• 15 Inaki N, Tsunezuka Y, Kawakami K et al.. Increased matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase activity and expression in heterotopically transplanted murine tracheas.  J Heart Lung Transplant. 2004;  23 218-227
• 16 Baluk P, Raymond W W, Ator E, Coussens L M, McDonald D M, Caughey G H. Matrix metalloproteinase-2 and -9 expression increases in Mycoplasma-infected airways but is not required for microvascular remodeling.  Am J Physiol Lung Cell Mol Physiol. 2004;  287 L307-L317
• 17 McMillan S J, Kearley J, Campbell J D et al.. Matrix metalloproteinase-9 deficiency results in enhanced allergen-induced airway inflammation.  J Immunol. 2004;  172 2586-2594
• 18 Joo N S, Lee D J, Winges K M, Rustagi A, Wine J J. Regulation of antiprotease and antimicrobial protein secretion by airway submucosal gland serous cells.  J Biol Chem. 2004;  279 38854-38860
• 19 Zhang Y, Reenstra W W, Chidekel A. Antibacterial activity of apical surface fluid from the human airway cell line Calu-3: pharmacologic alteration by corticosteroids and beta(2)-agonists.  Am J Respir Cell Mol Biol. 2001;  25 196-202
• 20 Babu P B, Chidekel A, Shaffer T H. Hyperoxia-induced changes in human airway epithelial cells: the protective effect of perflubron.  Pediatr Crit Care Med. 2005;  6 188-194
• 21 Miller T L, Touch S M, Shaffer T H. Matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase expression profiles in tracheal aspirates do not adequately reflect tracheal or lung tissue profiles in neonatal respiratory distress: observations from an animal model.  Pediatr Crit Care Med. 2006;  7 63-69
• 22 Bhutani V K, Shaffer T H. Effect of intermittent positive pressure application on the bulk modulus of the developing rabbit trachea.  Respiration. 1981;  41 192-198
• 23 Bhutani V K, Rubenstein D, Shaffer T H. Pressure-induced deformation in immature airways.  Pediatr Res. 1981;  15 829-832
• 24 Bhutani V K, Ritchie W G, Shaffer T H. Acquired tracheomegaly in very preterm neonates.  Am J Dis Child. 1986;  140 449-452
• 25 Deoras K S, Wolfson M R, Bhutani V K, Shaffer T H. Structural changes in the tracheae of preterm lambs induced by ventilation.  Pediatr Res. 1989;  26 434-437
• 26 Bhutani V K, Shaffer T H, Abbasi S, Spitzer A R, Fox W W. Effect of high-frequency jet ventilation on preterm and rabbit tracheal mechanics.  Pediatr Pulmonol. 1986;  2 327-331
• 27 Danan C, Jarreau P H, Franco M L et al.. Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia.  Am J Physiol Lung Cell Mol Physiol. 2002;  283 L1086-L1093
• 28 Corbel M, Belleguic C, Boichot E, Lagente V. Involvement of gelatinases (MMP-2 and MMP-9) in the development of airway inflammation and pulmonary fibrosis.  Cell Biol Toxicol. 2002;  18 51-61
• 29 Duszyk M, Shu Y, Sawicki G, Radomski A, Man S F, Radomski M W. Inhibition of matrix metalloproteinase MMP-2 activates chloride current in human airway epithelial cells.  Can J Physiol Pharmacol. 1999;  77 529-535
• 30 Vliagoftis H, Schwingshackl A, Milne C D et al.. Proteinase-activated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cells.  J Allergy Clin Immunol. 2000;  106 537-545
• 31 Atkinson J J, Senior R M. Matrix metalloproteinase-9 in lung remodeling.  Am J Respir Cell Mol Biol. 2003;  28 12-24
• 32 D'Ortho M P, Jarreau P H, Delacourt C et al.. Matrix metalloproteinase and elastase activities in LPS-induced acute lung injury in guinea pigs.  Am J Physiol. 1994;  266(3 Pt 1) L209-L216
• 33 Gibbs D F, Shanley T P, Warner R L, Murphy H S, Varani J, Johnson K J. Role of matrix metalloproteinases in models of macrophage-dependent acute lung injury. Evidence for alveolar macrophage as source of proteinases.  Am J Respir Cell Mol Biol. 1999;  20 1145-1154
• 34 Keck T, Balcom J Ht, Fernandez-del Castillo C, Antoniu B A, Warshaw A L. Matrix metalloproteinase-9 promotes neutrophil migration and alveolar capillary leakage in pancreatitis-associated lung injury in the rat.  Gastroenterology. 2002;  122 188-201
• 35 Vermaelen K Y, Cataldo D, Tournoy K et al.. Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma.  J Immunol. 2003;  171 1016-1022
• 36 Savov J D, Brass D M, Berman K G, McElvania E, Schwartz D A. Fibrinolysis in LPS-induced chronic airway disease.  Am J Physiol Lung Cell Mol Physiol. 2003;  285 L940-L948
• 37 Cataldo D D, Tournoy K G, Vermaelen K et al.. Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation.  Am J Pathol. 2002;  161 491-498