Particulate Matter From Saudi Arabia Induces Genes Involved in Inflammation, Metabolic Syndrome and Atherosclerosis

Airborne particulate matter (PM) exposure is a major environmental health concern and is linked to metabolic disorders, such as cardiovascular diseases (CVD) and diabetes, which are on the rise in the Kingdom of Saudi Arabia. This study investigated changes in mouse lung gene expression produced by administration of PM10 collected from Jeddah, Saudi Arabia. FVB/N mice were exposed to 100 μg PM10 or water by aspiration and euthanized 24 h later. The bronchoalveolar lavage fluid (BALF) was collected and analyzed for neutrophil concentration and tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels. RNA was extracted from lungs and whole transcript was analyzed using Affymetrix Mouse Gene 1.0 ST Array. Mice exposed to PM10 displayed an increase in neutrophil concentration and elevated TNF-α and IL-6 levels. Gene expression analysis revealed that mice exposed to PM10 displayed 202 genes that were significantly upregulated and 40 genes that were significantly downregulated. PM10 induced genes involved in inflammation, cholesterol and lipid metabolism, and atherosclerosis. This is the first study to demonstrate that Saudi Arabia PM10 increases in vivo expression of genes located in pathways associated with diseases involving metabolic syndrome and atherosclerosis.

[1]  A. Peters,et al.  Particulate Matter Air Pollution and Cardiovascular Disease: An Update to the Scientific Statement From the American Heart Association , 2010, Circulation.

[2]  P. Portincasa,et al.  Oxidized LDL Receptor 1 gene polymorphism in patients with Metabolic Syndrome , 2013, European journal of clinical investigation.

[3]  R. Kloner,et al.  Air pollution and cardiovascular injury epidemiology, toxicology, and mechanisms. , 2008, Journal of the American College of Cardiology.

[4]  P. Maciejczyk,et al.  Source Apportionment and Elemental Composition of PM2.5 and PM10 in Jeddah City, Saudi Arabia. , 2012, Atmospheric pollution research.

[5]  A. Mantovani,et al.  IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. , 2003, Trends in immunology.

[6]  A. Whitehead,et al.  Serum amyloid A, the major vertebrate acute-phase reactant. , 1999, European journal of biochemistry.

[7]  Zhang Ju-hong,et al.  Variations of six transmembrane epithelial antigen of prostate 4 (STEAP4) gene are associated with metabolic syndrome in a female Uygur general population. , 2010, Archives of medical research.

[8]  William Arbuthnot Sir Lane,et al.  Mouse serum amyloid A protein (SAA5) structure and expression. , 1994, Journal of Biological Chemistry.

[9]  Xavier Querol,et al.  Comparative PM10-PM2.5 source contribution study at rural, urban and industrial sites during PM episodes in Eastern Spain. , 2004, The Science of the total environment.

[10]  J. Mehta,et al.  Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1): a critical player in the development of atherosclerosis and related disorders. , 2006, Cardiovascular research.

[11]  J. Gromada,et al.  Activation of liver X receptors and retinoid X receptors induces growth arrest and apoptosis in insulin-secreting cells. , 2007, Endocrinology.

[12]  S. Rajagopalan,et al.  Air Pollution–Mediated Susceptibility to Inflammation and Insulin Resistance: Influence of CCR2 Pathways in Mice , 2013, Environmental health perspectives.

[13]  A. Russell,et al.  Sensitivity of Air Pollution-Induced Premature Mortality to Precursor Emissions under the Influence of Climate Change , 2010, International journal of environmental research and public health.

[14]  Michael Jerrett,et al.  The Association Between Chronic Exposure to Traffic-Related Air Pollution and Ischemic Heart Disease , 2012, Journal of toxicology and environmental health. Part A.

[15]  Benjamin M. Bolstad,et al.  affy - analysis of Affymetrix GeneChip data at the probe level , 2004, Bioinform..

[16]  D. Curiel,et al.  Inhibition of tumor necrosis factor alpha decreases inflammation and prolongs adenovirus gene expression in lung and liver. , 1998, Human gene therapy.

[17]  Kaarle Hämeri,et al.  Particulate matter air pollution and respiratory symptoms in individuals having either asthma or chronic obstructive pulmonary disease: a European multicentre panel study , 2012, Environmental Health.

[18]  C. Klein,et al.  Tumor Necrosis Factor-α-induced Adipose-related Protein (TIARP), a Cell-surface Protein That Is Highly Induced by Tumor Necrosis Factor-α and Adipose Conversion* , 2001, The Journal of Biological Chemistry.

[19]  J. Pennings,et al.  Gene Expression Pattern in Spontaneously Hypertensive Rats Exposed to Urban Particulate Matter (EHC-93) , 2005, Inhalation toxicology.

[20]  R. Frikke-Schmidt Context-dependent and invariant associations between APOE genotype and levels of lipoproteins and risk of ischemic heart disease: a review. , 2000, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[21]  C. Klein,et al.  Tumor necrosis factor-alpha-induced adipose-related protein (TIARP), a cell-surface protein that is highly induced by tumor necrosis factor-alpha and adipose conversion. , 2001, The Journal of biological chemistry.

[22]  J. Mehta,et al.  Deletion of LOX-1 Reduces Atherogenesis in LDLR Knockout Mice Fed High Cholesterol Diet , 2007, Circulation research.

[23]  F. Cunha,et al.  Tumour necrosis factor-alpha mediates neutrophil migration to the knee synovial cavity during immune inflammation. , 2004, European journal of pharmacology.

[24]  M. Ackermann,et al.  Endotoxin tolerance in rats: expression of TNF-alpha, IL-6, IL-10, VCAM-1 AND HSP 70 in lung and liver during endotoxin shock. , 1999, Cytokine.

[25]  G. Rossi,et al.  Urban Air Pollution and Emergency Visits for Respiratory Complaints in Pisa, Italy , 2007, Journal of toxicology and environmental health. Part A.

[26]  W. Zin,et al.  Roles of oxidative stress in signaling and inflammation induced by particulate matter , 2010, Cell Biology and Toxicology.

[27]  Barbara Heude,et al.  Ambient air pollution and low birthweight: a European cohort study (ESCAPE). , 2013, The Lancet. Respiratory medicine.

[28]  T. Kumosani,et al.  The State of Nutrition in Saudi Arabia , 2000, Nutrition and health.

[29]  M. Cybulsky,et al.  A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. , 2001, The Journal of clinical investigation.

[30]  M. Alama,et al.  Cardiovascular diseases in Saudi Arabia , 2011 .

[31]  M. Inoue,et al.  Long-term exposure to particulate matter in relation to mortality and incidence of cardiovascular disease: the JPHC Study. , 2013, Journal of atherosclerosis and thrombosis.

[32]  Y. Miller,et al.  Pulmonary Prostacyclin Synthase Overexpression Chemoprevents Tobacco Smoke Lung Carcinogenesis in Mice , 2004, Cancer Research.

[33]  S. Rajagopalan,et al.  Long-term exposure to ambient fine particulate pollution induces insulin resistance and mitochondrial alteration in adipose tissue. , 2011, Toxicological sciences : an official journal of the Society of Toxicology.

[34]  N. Donato,et al.  Tumor necrosis factor α: a multifaceted peptide hormone , 1989 .

[35]  L. Veronesi,et al.  [Particulate matter (PM10) air pollution, daily mortality, and hospital admissions: recent findings]. , 2006, Igiene e sanita pubblica.

[36]  A. K. Osman,et al.  Obesity: an emerging problem in Saudi Arabia. Analysis of data from the National Nutrition Survey. , 2007, Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit.

[37]  M. M. Nasralla,et al.  Air pollution in the semitropical Saudi urban area , 1983 .

[38]  M. Schivo,et al.  Diabetes and the Metabolic Syndrome: Possibilities of a New Breath Test in a Dolphin Model , 2013, Front. Endocrinol..

[39]  Serum amyloid A, phospholipase A2-IIA and C-reactive protein as inflammatory biomarkers for prostate diseases , 2013, Inflammation Research.

[40]  M. Rosen,et al.  Gene expression profiling in the lung and liver of PFOA-exposed mouse fetuses. , 2007, Toxicology.

[41]  Chun-Yuh Yang,et al.  Short-Term Effects of Fine Particulate Air Pollution on Emergency Room Visits for Cardiac Arrhythmias: A Case-Crossover Study in Taipei , 2013, Journal of toxicology and environmental health. Part A.

[42]  L. Barrozo,et al.  The impact of atmospheric particulate matter on cancer incidence and mortality in the city of São Paulo, Brazil. , 2012, Cadernos de saude publica.

[43]  M. Alqahtani,et al.  Genotoxicity of Air Borne Particulates Assessed by Comet and the Salmonella Mutagenicity Test in Jeddah, Saudi Arabia , 2007, International journal of environmental research and public health.

[44]  Errol M. Thomson,et al.  Mapping Acute Systemic Effects of Inhaled Particulate Matter and Ozone: Multiorgan Gene Expression and Glucocorticoid Activity , 2013, Toxicological sciences : an official journal of the Society of Toxicology.

[45]  A. A. Farooqui Lipid Mediators in Metabolic Syndrome and Neurological Disorders , 2013 .

[46]  Jun Wu,et al.  Asthma Morbidity and Ambient Air Pollution: Effect Modification by Residential Traffic-Related Air Pollution , 2012, Epidemiology.

[47]  M. Khoder,et al.  Gene expression profiling and pathway analysis of human bronchial epithelial cells exposed to airborne particulate matter collected from Saudi Arabia. , 2012, Toxicology and applied pharmacology.

[48]  Gordon K. Smyth,et al.  limma: Linear Models for Microarray Data , 2005 .

[49]  J. Mehta,et al.  Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer , 2011, PloS one.

[50]  M. Gelb,et al.  Groups IV, V, and X Phospholipases A2s in Human Neutrophils , 2002, The Journal of Biological Chemistry.

[51]  J. Hogg,et al.  Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques. , 2008, American journal of physiology. Heart and circulatory physiology.

[52]  J. Goldstein,et al.  Membrane-bound domain of HMG CoA reductase is required for sterol-enhanced degradation of the enzyme , 1985, Cell.

[53]  A. Baccarelli,et al.  Integrative Analysis of miRNA and inflammatory gene expression after acute particulate matter exposure. , 2013, Toxicological sciences : an official journal of the Society of Toxicology.

[54]  M. Schladweiler,et al.  Cardiovascular and thermoregulatory effects of inhaled PM-associated transition metals: a potential interaction between nickel and vanadium sulfate. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[55]  R. Ross,et al.  Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[56]  Kazuhiko Ito,et al.  Cardiovascular Effects of Nickel in Ambient Air , 2006, Environmental health perspectives.

[57]  Luiz Fernando Costa Nascimento,et al.  Particulate matter and hospital admission due to arterial hypertension in a medium-sized Brazilian city. , 2013, Cadernos de saude publica.

[58]  N. Donato,et al.  Tumor necrosis factor alpha: a multifaceted peptide hormone. , 1989, Critical reviews in immunology.

[59]  A. Warsy,et al.  Overweight and obesity in Saudi females of childbearing age , 2003, International Journal of Obesity.

[60]  K. Ghoshal,et al.  Influenza Virus Infection Induces Metallothionein Gene Expression in the Mouse Liver and Lung by Overlapping but Distinct Molecular Mechanisms , 2001, Molecular and Cellular Biology.

[61]  G Valli,et al.  Source apportionment of PM10 and PM2.5 in Milan (Italy) using receptor modelling. , 2003, The Science of the total environment.

[62]  M. Carraway,et al.  Composition of Air Pollution Particles and Oxidative Stress in Cells, Tissues, and Living Systems , 2012, Journal of toxicology and environmental health. Part B, Critical reviews.

[63]  Edward D. Karoly,et al.  Comparison of Gene Expression Profiles Induced By Coarse, Fine, and Ultrafine Particulate Matter , 2011, Journal of toxicology and environmental health. Part A.

[64]  Michael C. Ostrowski,et al.  Ambient Air Pollution Exaggerates Adipose Inflammation and Insulin Resistance in a Mouse Model of Diet-Induced Obesity , 2009, Circulation.

[65]  P. Chau,et al.  A review of effects of particulate matter-associated nickel and vanadium species on cardiovascular and respiratory systems , 2009, International journal of environmental health research.

[66]  Katherine A. Fitzgerald,et al.  Serum Amyloid A Activates the NLRP3 Inflammasome and Promotes Th17 Allergic Asthma in Mice , 2011, The Journal of Immunology.

[67]  Daniel Krewski,et al.  Health Effects Associated With Exposure to Ambient Air Pollution , 2007, Journal of toxicology and environmental health. Part A.

[68]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[69]  Josep M. Guerrero,et al.  Melatonin inhibits expression of the inducible NO synthase II in liver and lung and prevents endotoxemia in lipopolysaccharide‐induced multiple organ dysfunction syndrome in rats , 1999, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[70]  Peter Höppe,et al.  Health effects of particles in ambient air. , 2004, International journal of hygiene and environmental health.

[71]  K. Aljabri,et al.  Prevalence of diabetes mellitus in a Saudi community , 2011, Annals of Saudi medicine.

[72]  Chun-Yuh Yang,et al.  Fine Particulate Air Pollution and Hospital Admissions for Myocardial Infarction in a Subtropical City: Taipei, Taiwan , 2013, Journal of toxicology and environmental health. Part A.

[73]  C. Zhang,et al.  Serum Amyloid A Directly Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice , 2011, Molecular medicine.

[74]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[75]  A. Nel,et al.  Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress , 2009, Particle and Fibre Toxicology.

[76]  R. Paschke,et al.  Serum amyloid A3 expression is stimulated by dexamethasone and interleukin-6 in 3T3-L1 adipocytes. , 2004, The Journal of endocrinology.

[77]  F. Bazzoni,et al.  The neutrophil as a cellular source of chemokines , 2000, Immunological reviews.

[78]  T. Kazi,et al.  Association of Environmental Toxic Elements in Biological Samples of Myocardial Infarction Patients at Different Stages , 2011, Biological Trace Element Research.

[79]  F. Foufelle,et al.  SREBP transcription factors: master regulators of lipid homeostasis. , 2004, Biochimie.

[80]  E. de Luca d'Alessandro,et al.  OVERWEIGHT AND OBESITY , 2007, Hormone Research in Paediatrics.

[81]  Sabit Cakmak,et al.  Long-Term Fine Particulate Matter Exposure and Mortality From Diabetes in Canada , 2013, Diabetes Care.

[82]  Michael Brauer,et al.  Associations of ambient air pollution with chronic obstructive pulmonary disease hospitalization and mortality. , 2013, American journal of respiratory and critical care medicine.

[83]  A. Bayram,et al.  Source apportionment of PM(10) and PM(2.5) using positive matrix factorization and chemical mass balance in Izmir, Turkey. , 2008, The Science of the total environment.