Health  Vol.5 No.10 B , October 2013
African Dust Storms Reaching Puerto Rican Coast Stimulate the Secretion of IL-6 and IL-8 and Cause Cytotoxicity to Human Bronchial Epithelial Cells (BEAS-2B)

African dust storm events (ADE) travel across theAtlantic Ocean(ADEAO) and reach the Puerto Rican coast (ADEPRC), potentially impacting air quality and human health. To what extent seasonal variations in atmospheric particulate matter (PM) size fractions, composition and sources trigger respiratory-adverse effects to Puerto Ricans is still unclear. In the present study, we investigated the pro-inflammatory and cytotoxic effects of PM samples harvested during ADEAO (PM10), ADEPRC (PM2.5 and PM10) and Non-ADE (Pre-and Post-ADEAO and Non-ADEPRC), using BEAS-2B cells. Endotoxins (ENX) in PM2.5 and PM10 extracts and traces of metals (TMET) in PM2.5 extracts were also examined. IL-6 and IL-8 secretion and cytotoxicity were used as endpoints. ADEAO and ADEPRC extracts were found to be more cytotoxic than Non-ADE and ADEAO were more toxic than ADEPRC extracts. PM10 extracts from ADEAO and Post-ADEAO caused significant secretion of IL-8. IL-6 and IL-8 secretion was higher following treatment with PM10 and PM2.5 ADEPRC than with Non-ADEPRC extracts. ENX levels were found to be higher in PM10 ADEAO than in the rest of the samples tested. TMET levels were higher in PM2.5 ADEPRC than in Non-ADEPRC extracts. Deferoxamine significantly reduced cytotoxicity and IL-6 and IL-8 secretion whereas Polymyxin B did not. TMET in PM2.5 fractions is a major determinant in ADEPRC-induced toxicity and work in conjunction with ENX to cause toxicity to lung cells in vitro. ENX and TMET may be responsible, in part, for triggering PM-respiratory adverse responses in susceptible and predisposed individuals.

Cite this paper: Rodríguez-Cotto, R. , Ortiz-Martínez, M. , Rivera-Ramírez, E. , Méndez, L. , Dávila, J. and Jiménez-Vélez, B. (2013) African Dust Storms Reaching Puerto Rican Coast Stimulate the Secretion of IL-6 and IL-8 and Cause Cytotoxicity to Human Bronchial Epithelial Cells (BEAS-2B). Health, 5, 14-28. doi: 10.4236/health.2013.510A2003.

[1]   Prospero, J.M. and Nees, R.T. (1977) Dust concentration in the atmosphere of the equatorial north Atlantic: Possible relationship to the Sahelian drought. Science, 196, 1196-1198.

[2]   Wittig, R., Konig, K., Schmidt, M. and Szarzynski, J. (2007) A study of climate change and anthropogenic impacts in West Africa. Environmental Science and Pollution Research, 14, 182-189.

[3]   Griffin, D.W. (2007) Atmospheric movement of microorganisms in clouds of desert dust and implications for human health. Clinical Microbiology Reviews, 20, 459-477.

[4]   Prospero, J.M. and Lamb, P.J. (2003) African droughts and dust transport to the Caribbean: Climate change implications. Science, 302, 1024-1027.

[5]   Griffin, D.W. and Seba, D.B. (2003) Atmospheric transport of mold spores in clouds of desert dust. Archives of Environmental Health, 58, 498-504.

[6]   Chiapello, I., Moulin, C. and Prospero, J.M. (2005) Understanding the long-term variability of African dust transport across the Atlantic as recorded in both Barbados surface concentrations and large-scale Total Ozone Mapping Spectrometer (TOMS) optical thickness. Journal of Geophysical Research, 110, D18S10.

[7]   Monteil, M.A. (2008) Saharan dust clouds and human health in the English-speaking Caribbean: What we know and don’t know. Environmental Geochemistry and Health, 30, 339-343.

[8]   Montealegre, F., Chardon, D. and Tarrats, H. (1993) Environmental factors precipitating bronchial asthma exacerbations in southern Puerto Rico: A pilot study. Journal of Asthma, 30, 219-227.

[9]   Reid, J.S., Kinney, J.E., Wastphal, D.L., Holben, B.N., Welton, E.J., Tsay, S.-C., et al. (2003) Analysis of measurements of Saharan dust by airborne and ground-based remote sensing methods during the Puerto Rico Dust Experiment (PRIDE). Journal of Geophysical Research, 108, 8586.

[10]   Jiménez-Vélez, B., Detrés,, Y., Armstrong, R.A. and Gioda, A. (2009) Characterization of African Dust (PM2.5) across the Atlantic Ocean during AEROSE 2004. Atmospheric Environment, 43, 2659-2664.

[11]   Trapp, J.M., Millero, F.J. and Prospero, J.M. (2010) Temporal variability of the elemental composition of African dust measured in trade wind aerosols at Barbados and Miami. Atmospheric Environment, 120, 71-82.

[12]   Ortiz-Martinez, M., Rivera-Ramirez, E., Mendez-Torres, L. and Jiménez-Vélez, B.D. (2010) Role of chemical and biological constituents of PM10 from Saharan dust in the exacerbation of asthma in Puerto Rico. Biodiversity Science for Humanity, Athens Institute for Educations & Research, 101-118.

[13]   Aust, A.E., Ball, J.C., Hu, A.A., Lighty, J.S., Smith, K.R., Straccia, A.M., et al. (2002) Particle characteristics responsible for effects on human lung epithelial cells. Research Report (Health Effects Institute), 110, 1-65.

[14]   Schlesinger, R.B., Kunzli, N., Hidy, G.M., Gotschi, T. and Jerrett, M. (2006) The health relevance of ambient particulate matter characteristics: Coherence of toxicological and epidemiological inferences. Inhalation Toxicology, 18, 95-125.

[15]   Schwarze, P.E., Ovrevik, J., Hetland, R.B., Becher, R., Cassee, F.R., Lag, M., et al. (2007) Importance of size and composition of particles for effects on cells in vitro. Inhalation Toxicology, 19, 17-22.

[16]   Duzgoren-Aydin, N.S. (2008) Health effects of atmospheric particulates: A medical geology perspective. Journal of Environmental Science and Health Part C: Environmental Carcinogenesis & Ecotoxicology Reviews, 26, 1-39.

[17]   Demerjian, K.L. and Mohnen, V.A. (2008) Synopsis of the temporal variation of particulate matter composition and size. Journal of the Air & Waste Management Association, 58, 216-233.

[18]   Bell, M.L., HEI Health Review Committee (2012) Assessment of the health impacts of particulate matter characteristics. Research Report (Health Effects Institute), 161, 5-38.

[19]   Garrison, V.H., Foreman, W.T., Genualdi, S.D., Griffin, W., Kellogg, C.A., Majewski, et al. (2006) Saharan dusta carrier of persistent organic pollutants, metals and microbes to the Caribbean? International Journal of Tropical Biology, 54, 9-21.

[20]   Morris, V. (2010) Personal Communication. Howard University, Washington DC.

[21]   Costa, D.L. and Dreher, K.L.(1997) Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. Environmental Health Perspectives, 105, 1053-1060.

[22]   Molinelli, A.R., Santacana, G.E., Madden, M.C. and Jiménez, B.D. (2006) Toxicity and metal content of organic solvent extracts from airborne particulate matter in Puerto Rico. Environmental Research, 102, 314-325.

[23]   Chen, L.C. and Lippmann, M. (2009) Effects of metals within ambient air particulate matter (PM) on human health. Inhalation Toxicology, 21, 1-31.

[24]   Lippmann, M. And Chen, L.C. (2009) Health effects of concentrated ambient air particulate matter (CAPs) and its components. Critical Reviews in Toxicology, 39, 865-913.

[25]   Ma, J. Y. and Ma, J. K. (2002) The dual effect of the particulate and organic components of diesel exhaust particles on the alteration of pulmonary immune/inflammatory responses and metabolic enzymes. Journal of Environmental Science and Health Part C: Environmental Carcinogenesis & Ecotoxicology Reviews, 20, 117-147.

[26]   Becker, S., Mundandhara, S., Devlin, R.B. and Madden, M. (2005) Regulation of cytokine production in human alveolar macrophages and airway epithelial cells in response to ambient air pollution particles: further mechanistic studies. Toxicology and Applied Pharmacology, 207, 269-275.

[27]   Schwartz, D.A. (2001) Does inhalation of endotoxin cause asthma? American Journal of Respiratory and Critical Care Medicine, 163, 305-313.

[28]   de Kok, T.M., Driece, H.A., Hogervorst, J.G. and Briedé, J.J. (2006) Toxicological assessment of ambient and traffic-related particulate matter: A review of recent studies. Mutation Research, 613, 103-122.

[29]   Valavanidis, A., Fiotakis, K. and Vlachogianni, T. (2008) Airborne particulate matter and human health: Toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. Journal of Environmental Science and Health Part C: Environmental Carcinogenesis & Ecotoxicology Reviews, 26, 339-362.

[30]   D’Amato, G. and Cecchi, L. (2008) Effects of climate change on environmental factors in respiratory allergic diseases. Clinical & Experimental Allergy, 38, 1264-1274.

[31]   Huang, Y.C., Li, Z., Carter, J.D., Soukup, J.M., Schwartz, D.A. and Yang, I.V. (2009) Fine ambient particles induce oxidative stress and metal binding genes in human alveolar macrophages. American Journal of Respiratory Cell and Molecular Biology, 41, 544-552.

[32]   Brook, R.D., Rajagopalan, S.C., Pope III, A., Brook, J.R., Bhatnagar, A. and Diez-Roux, A.V., et al. (2010) Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation, 2331-2377.

[33]   Jie, Y., Ismail, N.H., Jie, X. and Isa, Z.M. (2011) Do indoor environments influence asthma and asthma-related symptoms among adults in homes? A review of the literature. Toxicology, 299, 125-132.

[34]   de Longueville, F., Ozer, P., Doumbia, S. and Henry, S. (2012) Desert dust impacts on human health: An alarming worldwide reality and a need for studies in West Africa. International Journal of Biometeorology, 3, 1-19.

[35]   Van Berlo, D., Hullmann, M. and Schins, R.P. (2012) Toxicology of ambient particulate matter. Molecular, Clinical and Environmental Toxicology: Experientia Supplementum, 101, 165-217.

[36]   Weichenthal, S. (2012) Selected physiological effects of ultrafine particles in acute cardiovascular morbidity. Environmental Research, 115, 26-36.

[37]   Hetland, R.B., Cassee, F.R., Refsnes, M., Schwarze, P.E., Lag, M., Boere, A.J., et al. (2004) Release of inflammatory cytokines, cell toxicity and apoptosis in epithelial lung cells after exposure to ambient air particles of different size fractions. Toxicology in Vitro, 18, 203-212.

[38]   Hetland, R., Cassee, F., Lag, M., Refsnes, M., Dybing, E. and Schwarze, P.E. (2005) Cytokine release from alveolar macrophages exposed to ambient particulate matter: Heterogeneity in relation to size, city and season. Particle and Fibre Toxicology, 2, 1-15.

[39]   Abbas, I., Saint-Georges, F., Billet, S., Verdin, A., Mulliez, P., Shirali, P., et al. (2008) Air pollution particulate matter (PM2.5)-induced gene expression of volatile organic compound and/or polycyclic aromatic hydrocarbon-metabolizing enzymes in an in vitro coculture lung model. Toxicology in Vitro, 23, 37-46.

[40]   Maier, K.L., Alessandrini, F., Beck-Speier, I., Hofer, T.P., Diabaté, S., Bitterle, E., et al. (2008) Health effects of ambient particulate matter-biological mechanisms and inflammatory responses to in vitro and in vivo particle exposures. Inhalation Toxicology, 20, 319-337.

[41]   Billet, S., Abbas, I., Le Goff, J., Verdin, A., Andre′, V., Lafargue, P.-E., et al. (2008) Genotoxic potential of polycyclic aromatic hydrocarbons-coated onto airborne particulate matter (PM2.5) in human lung epithelial A549 cells. Cancer Letters, 270, 144-155.

[42]   Shoenfelt, J., Mitkus, R.J., Zeisler, R., Spatz, R.O., Powell, J., Fenton, M.J., et al. (2009) Involvement of TLR2 and TLR4 in inflammatory immune responses induced by fine and coarse ambient air particulate matter. Journal of Leukocyte Biology, 86, 303-312.

[43]   Danielsen, P.H., Loft, S., Jacobsen, N.R., Jensen, K.A., Autrup, H., Ravanat, J.L., et al. (2010) Oxidative stress, inflammation, and DNA damage in rats after intratracheal instillation or oral exposure to ambient air and wood smoke particulate matter. Toxicological Sciences, 118, 574-585.

[44]   Zhu, J. and Mohan, C. (2010) Toll-like receptor signaling pathways-therapeutic opportunities. Mediators of Inflammation, 2010, Article ID: 78123.

[45]   Aust, A.E., Cook, P.M. and Dodson, R.F. (2011) Morphological and chemical mechanisms of elongated mineral particle toxicities. Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 14, 40-75.

[46]   Dergham, M., Lepers, C., Verdin, A., Billet, S., Cazier, F., Courcot, D., et al. (2012) Prooxidant and proinflammatory potency of air pollution particulate matter (PM2.5-0.3) produced in rural, urban, or industrial surroundings in human bronchial epithelial cells (BEAS-2B). Chemical Research in Toxicology, 25, 904-919.

[47]   Li, Z., Tighe, R.M., Feng, F., Ledford, J.G. & Hollingsworth, J.W. (2013) Genes of innate immunity and the biological response to inhaled ozone. Journal of Biochemical and Molecular Toxicology, 27, 3-16.

[48]   Rossi, O.V., Kinnula, V.L., Tienari, J. and Huhti, E. (1993) Association of severe asthma attacks with weather, pollen, and air pollutants. Thorax, 48, 244-248.

[49]   Ledogar, R.J., Penchaszadeh, A., Garden, C.C. and Iglesias, G. (2000) Asthma and Latino cultures: Different prevalence reported among groups sharing same environment. American Journal of Public Health, 90, 929-935.

[50]   Gyan, K., Henry, W., Lacaille, S., Laloo, A., Lamsee-Ebanks, C., McKay, S., et al. (2004) African dust clouds are associated with increased paediatric asthma accident and emergency admissions on the Caribbean island of Trinidad. International Journal of Biometeorology, 49, 371-376.

[51]   Prospero, J.M., Blades, E., Naidu, R., Mathison, G., Thani H. and Lavoie, M.C. (2008) Relationship between African dust carried in the Atlantic trade winds and surges in pediatric asthma attendances in the Caribbean. International Journal of Biometeorology, 52, 823-832.

[52]   Karakatsani, A., Analitis, A., Perifanou, D., Ayres, J.G., Harrison, R.M., Kotronarou, A., et al. (2012) Particulate matter and air pollution and respiratory symptoms in individuals having either asthma or chronic obstructive pulmonary disease: A European multicentre panel study. Environmental Health, 11, 75.

[53]   Wang, G., Jiang, R., Zhao, Z. and Song, W. (2013) Effects of ozone and the particulate matter (PM2.5) on rat system inflammation and cardiac function. Toxicology Letters, 217, 23-33.

[54]   Zora, J.E., Sarnat, S.E., Raysoni, A.U., Johnson, B.A., Li, W.W., Greenwald, R., et al. (2013) Associations between urban air pollution and pediatric asthma control in El Paso, Texas. Science of the Total Environment, 448, 56-65.

[55]   Li, N., Hao, M., Phalen, R., Hinds, W. and Nel, A. (2003) Particulate air pollutants and asthma A paradigm for the role of oxidative stressing PM-induced adverse health affects. Clinical Immunology, 109, 250-265.

[56]   Soukup, J.M. and Becker, S. (2001) Human alveolar macrophage responses to air pollution particulates are associated with insoluble components of coarse material, including particulate endotoxin. Toxicology and Applied Pharmacology, 171, 20-26.

[57]   Veranth. J.M., Reilly, C.A., Veranth, M.M., Moss, T.A., Langelier, C.R., Lanza, D.L., et al. (2004) Inflammatory cytokines and cell death in BEAS-2B lung cells treated with soil dust, lipopolysaccharide, and surface-modified particles. Toxicological Sciences, 82, 88-96.

[58]   Valko, M., Morris, H. and Cronin, M.T.D. (2005) Metals, toxicity and oxidative stress. Current Medicinal Chemistry, 11, 1161-1208.

[59]   Gualtieri, M., Ovrevik. J., Holme, J.A., Grazia-Perrone, M., Bolzacchini. E., Schwarze, P.E., et al. (2010) Differences in cytotoxicity versus pro-inflammatory potency of different PM fractions in human epithelial lung cells. Toxicology in Vitro, 24, 29-39.

[60]   Riley, M.R., Boesewetter, D.E., Kim, A.M. and Sirvent, F.P. (2003) Effects of metals Cu, Fe, Ni, V, and Zn on rat lung epithelial cells. Toxicology, 190, 171-184.

[61]   Carter, J.D., Ghio, A., Samet, J. and Devlin, R.B. (1997) Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal dependent. Toxicology and Applied Pharmacology, 146, 180-188.

[62]   Reyes, D., Rosario, O., Rodríguez, J.F. and Jiménez, B.D. (2010) Toxic evaluation of organic extracts from airborne particulate matter in Puerto Rico. Environmental Health Perspectives, 108, 635-640.

[63]   Acevedo-Figueroa, D., Rodríguez-Sierra, C.J. and Jiménez-Vélez, B.D. (2006) Concentrations of Ni and V, other heavy metals, arsenic, elemental and organic carbon in atmospheric fine particles (PM2.5) from Puerto Rico. Toxicology & Industrial Health, 22, 87-99.

[64]   Gioda, A., Pérez, U., Rosa, Z. and Jiménez-Vélez, B.D. (2006) Concentrations of trace elements in airborne PM10 from Jobos Bay National Estuary, Puerto Rico. Water, Air, and Soil Pollution, 174, 141-159.

[65]   Gioda, A., Pérez, U., Rosa, Z. and Jiménez-Vélez, B.D. (2007) Particulate matter (PM10 and PM2.5) from different areas of Puerto Rico. Fresenius Environmental Bulletin, 16, 861-868.

[66]   Gioda, A., Fuentes-Mattei, E. and Jiménez-Vélez, B. (2011) Evaluation of cytokine expression in BEAS cells exposed to fine particulate matter (PM2.5) from specialized indoor environments. International Journal of Environmental Health Research, 21, 106-119.

[67]   Jiménez-Vélez, B.D., Gioda, A. and Fuentes-Mattei, E. (2006) Organic and aqueous extracts from particulate matter (PM2.5) and their effects on the immunological response of BEAS cells. In: Collery, P., Ed., Metal Ions in Biology and Medicine, John Libbey Eurotext, Paris, 267-272.

[68]   Fuentes-Mattei, E., Rivera, E., Gioda, A., Sanchez-Rivera, D., Roman-Velazquez, F.R. and Jiménez-Vélez. B.D. (2010) Use of human bronchial epithelial cells (BEAS-2B) to study immunological markers resulting from exposure to PM2.5 organic extract from Puerto Rico. Toxicology and Applied Pharmacology, 243, 381-389.

[69]   Centers for Disease Control and Prevention, National Center for Health Statistics. (2011) Asthma prevalence, health care use, and mortality: United States, 2005-2009. National Health Statistics Reports.

[70]   Centers for Disease Control and Prevention, National Center for Health Statistics. (2012) National surveillance of Asthma: United States, 2001-2010. Vital and Health Statistics. Series 3.

[71]   Kanatani, K.T., Ito, I., Al-Delaimy, W.K., Adachi, Y., Mathews, W.C. and Ramsdell, J.W. (2010) Desert dust exposure is associated with increased risk of asthma hospitalization in children. American Journal of Respiratory and Critical Care Medicine, 182, 1475-1481.

[72]   Li, S., Williams, G., Jalaludin, B. and Baker, P. (2012) Panel studies of air pollution on children’s lung function and respiratory symptoms: A literature review. Journal of Asthma, 49, 895-910.

[73]   Tam, W.W., Wong, T.W., Wong, A.H. and Hui, D.S. (2012) Effect of dust storm events on daily emergency admission for respiratory diseases. Respirology, 17, 143-148.

[74]   Manzano-Leon, N., Quintana, R., Sanchez, B., Serrano, J., Vega, E., Vazquez-Lopez, et al. (2013) Variation in the composition and in vitro pro-inflammatory effect of urban particulate matter from different sites. Journal of Biochemical and Molecular Toxicology, 27, 87-97.

[75]   Asthma in Puerto Rico: BRFSS analysis for the year 2000. (2002) Asthma Statistical Report.

[76]   Heinrich, J. and Slama, R. (2007) Fine particles, a major threat to children. International Journal of Hygiene and Environmental Health, 210, 617-622.

[77]   Samoli, E., Nastos, P.T., Paliatsos, A.G., Katsouyanni, K. and Priftis, K.N. (2011) Acute effects of air pollution on pediatric asthma exacerbation: Evidence of association and effect modification. Environmental Research, 11, 418-424.

[78]   Saravia, J., Lee, G.I., Lomnicki, S., Dellinger B. and Cormier, S.A. (2013) Particulate matter containing environmentally persistent free radicals and adverse infant respiratory health effects: A review. Journal of Biochemical and Molecular Toxicology, 27, 56-68.

[79]   Chen, W., Boutaoui, N., Brehm, J.M., Han, Y.-Y., Schmitz, C., Cressley, A., et al. (2013) ADCYAP1R1 and asthma in Puerto Rican children. American Journal of Respiratory and Critical Care Medicine, 187, 584-588.

[80]   Jovanovic, T., Norrholm, S.D., Davis, J., Mercer, K.B., Almli, L., Nelson, A., et al. (2012) PAC1 receptor (AD-CYAP1R1) genotype is associated with dark-enhanced startle in children. Molecular Psychiatry, 18, 742-743.

[81]   Ramsey, S., Delling, M. and Clapham, D.E. (2006) An introduction to TRP channels. Annual Review of Physiology, 68, 619-647.

[82]   Nilius, B. (2007) TRP channels in disease. Biochimica et Biophysica Acta, 1772, 805-812.

[83]   Nilius, B., Owsianik, G., Voets, T. and Peters, J.A. (2007) Transient receptor cation channels in disease. Physiological Review, 87, 165-217.

[84]   Ghelfi, E., Rhoden, C.R., Wellenius, G.A., Lawurence, J. and Gonzalez-Flecha, B. (2008) Cardiac oxidative stress and electrophysiological changes in rats exposed to concentrated ambient particles are mediated by TRP-dependent pulmonary reflexes. Toxicological Sciences, 102, 328-336.

[85]   Deering-Rice, C.E., Romero, E.G., Shapiro, D., Hughen, R.W., Light, A.R., Yost, G.S., et al. (2011) Electrophilic components of diesel exhaust particles (DEP) activate transient receptor potential ankyrin-1 (TRPA1): A probable mechanism of cute pulmonary toxicity for DEP. Chemical Research in Toxicology, 24, 950-959.

[86]   Deering-Rice, C.E., Johansen, M.E., Roberts, J.K., Thomas, K.C., Romero, E.G., Lee, J., et al. (2012) Transient receptor potential vanilloid-1 (TRPV1) is a mediator of lung toxicity for coal fly ash particulate material. Molecular Pharmacology, 81, 411-419.

[87]   Vennekens, R. (2011) Emerging concepts for the role of TRP channels in the cardiovascular system. The Journal of Physiology, 589, 1527-1534.

[88]   Fariss, M.W., Gilmour, M.I., Reilly, C.A., Liedtke, W. and Ghio, A. (2013) Emerging mechanistic targets in lung injury induced by combustion-generated particles. Toxicological Sciences, 132, 253-267.

[89]   Agopyan, N., Bhatti, T., Yu, S. and Simon, S.A. (2003) Vanilloid receptor activation by 2and 10-μm particles induces responses leading to apoptosis in human airway epithelial cells. Toxicology and Applied Pharmacology, 192, 21-35.

[90]   Agopyan, N., Li, L., Yu, S. and Simon, S.A. (2003) Negatively charged 2-and 10-μM particles activate vanilloid receptors, increase cAMP, and induce cytokine release. Toxicology and Applied Pharmacology, 186, 63-76.

[91]   Inoue, R., Jensen, J.L., Shi, J., Morita, H., Nishida, M., Honda, A., et al. (2006) Transient receptor potential channels in cardiovascular function and disease. Circulation Research, 99, 119-131.

[92]   Segura-Valdez, L., Pardo, A., Caxiola, M., Uhal, B.D., Becerril, C. and Selma, M. (2000) Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD. Chest, 117, 684-694.

[93]   Joos, L., He, J.Q., Shepherdson, M.B., Connett, J.E., Anthonisen, N.R., Pare, P.D., et al. (2002) The role of matrix metalloproteinase polymorphysms in the rate of decline in lung function. Human Molecular Genetics, 11, 569-576.

[94]   Atkinson, J. and Senior, R.M. (2003) Matrix metalloproteinase-9 in lung remodeling. American Journal of Respiratory Cell and Molecular Biology, 8, 12-24.

[95]   Kong, M.Y.F., Gaggar, A., Li, Y., Winkler, M., Blalock, J.E. and Clancy, J. (2009) Matrix metalloproteinase activity in pediatric acute lung injury. International Journal of Medical Sciences, 61, 9-17.!po=73.0769

[96]   Zhu, G., Gulsvik, A., Bakke, P., Ghatta, S., Anderson, W., Lomas, D.A., et al (ICGN Investigators). (2009) Associaiton of TRPV4 gene polymorphism with chronic obstructive pulmonary disease. Human Molecular Genetics, 18, 2053-2062.

[97]   Smit, L.A.M., Kogevinas, M., Anto, J.M., Bouzigon, E., Gonzalez, J.R., Moual, N.L., et al. (2012) Transient receptor potential genes, smoking, occupational exposures and cough in adults. Respiratory Research, 13, 26.

[98]   Cantero-Recasens, G., Gonzalez, J.R., Fandos, C., DuranTauleria, E., Smit, L.A.M., Kauffmann, F., et al. (2010) Loss of function of transient receptor potential vanilloid 1 (TRPV1) genetic variant is associated with lower risk of active childhood asthma. The Journal of Biological Chemistry, 285, 27532-27535.

[99]   Ghio, A.J., Stonehuerner, J., Pritchard, R.J., Piantadosi, C.A., Quigley, D.R., Dreher, K.L., et al. (1996) Humiclike substances in air pollution particles correlate with concentration of transition metals and oxidant generation. Inhalation Toxicology, 8, 479-494.

[100]   Ghio, A.J., Carraway, M.S. and Madden, M.C. (2012) Composition of air pollution particles and oxidative stress in cells, tissues, and living systems. Journal of Toxicology and Environmental Health, Part B: Critical Reviews, 15, 1-21.