@2024 Afarand., IRAN
ISSN: 2008-2630 Iranian Journal of War & Public Health 2015;7(1):35-42
ISSN: 2008-2630 Iranian Journal of War & Public Health 2015;7(1):35-42
CXCL10 Gene Expression in the Lung Tissue of Sulfur Mustard-Exposed Patients with Long-Term Pulmonary Complications
ARTICLE INFO
Article Type
Original ResearchAuthors
Nikounezhad M. (1 )Ghazanfari T. (* )
Askari N. (2 )
Zarnani A.H. (3 )
Gohari Moghaddam K. (4 )
Mirafsharieh A. (5 )
(* ) Immunoregulation Research Center, Shahed University, Tehran, Iran
(1 ) Immunology Department, Medicine Faculty, Shahed University, Tehran, Iran
(2 ) Biology Department, Basic Sciences Faculty, Shahid Bahonar University, Kerman, Iran
(3 ) Ibn-e-Sina Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
(4 ) Pulmonary Disease Department, Medicine Faculty, Tehran University of Medical Sciences, Tehran , Iran
(5 ) Pathology Department, Medicine Faculty, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Correspondence
Address: Immunoregulation Research Center, 4th Floor, Shahed University Research Centers Building, No. 1471, Corner of Mehr Alley, North Karegar Street, Enqelab Square, Tehran, IranPhone: +98 2166418216
Fax: +98 2166419752
tghazanfari@yahoo.com
Article History
Received: August 5, 2014Accepted: August 25, 2014
ePublished: February 19, 2015
ABSTRACT
Aims
Mustard gas is an alkalizing substance that can lead to damage to DNA and intracellular
enzymes. The aim of this study was to investigate the expression of CXCL10 in chemicallyinjured
veterans’ lung tissue.
Materials & Methods This case-control study was done on 16 lung paraffin blocks of individuals exposed to mustard gas and 7 lungs paraffin blocks not-exposed people as control group and with similar chronic pulmonary disorders in 2014. Real-Time PCR technique was used to measureCXCL10 expression in lung tissue. To measure the relative expression of genes CT Delta method was used. Data were analyzed using SPSS 20 software and Mann- Whitney test.
Findings Mean Delta CT of veteran samples was 7.37±3.58 and control group was 5.81±3.29 and no significant difference was observed between 2 groups and between exposed and nonexposed subgroups (p>0.05). CXCL10 gene expression pattern was same in exposed and notexposed group with similar pulmonary pathology.
Conclusion The level and pattern of CXCL10 expression is not different in lung tissue of two exposed and not-exposed with similar pulmonary pathology groups.
Materials & Methods This case-control study was done on 16 lung paraffin blocks of individuals exposed to mustard gas and 7 lungs paraffin blocks not-exposed people as control group and with similar chronic pulmonary disorders in 2014. Real-Time PCR technique was used to measureCXCL10 expression in lung tissue. To measure the relative expression of genes CT Delta method was used. Data were analyzed using SPSS 20 software and Mann- Whitney test.
Findings Mean Delta CT of veteran samples was 7.37±3.58 and control group was 5.81±3.29 and no significant difference was observed between 2 groups and between exposed and nonexposed subgroups (p>0.05). CXCL10 gene expression pattern was same in exposed and notexposed group with similar pulmonary pathology.
Conclusion The level and pattern of CXCL10 expression is not different in lung tissue of two exposed and not-exposed with similar pulmonary pathology groups.
CITATION LINKS
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[23]Chen H, Wang D, Wang X. Role of airway epithelium-origin chemokines and their receptors in COPD. J Epithel Biol Pharmacol. 2010;3:26-33.
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[26]Dong S, Zhang X, He Y, Xu F, Li D, Xu W, et al. Synergy of IL-27 and TNF-α in regulating CXCL10 expression in lung fibroblasts. Am J Respir Cell Mol Biol. 2013;48(4):518-30.
[27]Jiang D, Liang J, Hodge J, Lu B, Zhu Z, Yu S, et al. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J Clin Invest. 2004;114(2):291-9.
[28]Burdick MD, Murray LA, Keane MP, Xue YY, Zisman DA, Belperio JA, et al. CXCL11 attenuates bleomycin-induced pulmonary fibrosis via inhibition of vascular remodeling. Am J Respir Crit Care Med. 2005;171(3):261-8.
[29]Tager AM, Kradin RL, LaCamera P, Bercury SD, Campanella GS, Leary CP, et al. Inhibition of pulmonary fibrosis by chemokin IP10/CXCL10. Am J Respir Cell Mol Biol. 2004;31(4):395-404.
[30]Jiang D, Liang J, Guo R, Xie T, Kelly FL, Martinu T, et al. Long-term exposure of chemokine CXCL10 causes bronchiolitis-like inflammation. Am J Respir Cell Mol Biol. 2012;46(5):592-8.
[31]Agostini C, Calabrese F, Poletti V, Marcer G, Facco M, Miorin M, et al. CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis. Respir Res. 2005;22;6:20.
[32]Ghazanfari T, Yaraee R, Kariminia A, Ebtekar M, Faghihzadeh S, Vaez-Mahdavi MR, et al. Alterations in the serum levels of chemokines 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1471-6.
[33]Yaraee R, Ghazanfari T, Ebtekar M, Ardestani SK, Rezaei A, Kariminia A, et al. Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study. Int Immunopharmacol. 2009;9(13-14):1466-70.
[34]Yaraee R, Ghazanfari T, Faghihzadeh S, Mostafaie A, Soroush MR, Inai K, et al. Alterations in the serum levels of soluble L, P and E-selectin 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1477-81.
[35]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
[36]Ghanei M, Adibi I. Clinical review of mustard lung. Iran J Med Sci. 2007;32(2):58-65.
[37]Lari SM, Attaran D, Towhidi M. COPD Due to Sulfur Mustard (Mustard Lung). In: Ong KCh. Chronic Obstructive Pulmonary Disease - Current Concepts and Practice. Croatia: InTech; 2012. Pp. 231-238.
[38]Attaran D, Lari SM, Khajehdaluee M, Ayatollahi H, Towhidi M, Asnaashari A, et al. Highly sensitive C-reactive protein levels in Iranian patients with pulmonary complication of sulfur mustard poisoning and its correlation with severity of airway diseases. Hum Exp Toxicol. 2009;28(12):739-45.
[39]Attaran D, Lari SM, Towhidi M, Marallu HG, Ayatollahi H, Khajehdaluee M, et al. Interleukin-6 and airflow limitation in chemical warfare patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2010;5:335-40
[40]Pourfarzam S, Ghazanfari T, Merasizadeh J, Ghanei M, Azimi G, Araghizadeh H, et al. Long-term pulmonary complications in sulfur mustard victims of Sardasht, Iran. Toxin Rev. 2009;28(1):8-13.
[41]Ghanei M, Amiri S, Akbari H, Kosari F, Khalili AR, Alaeddini F, et al. Correlation of sulfur mustard exposure and tobacco use with expression (immunoreactivity) of p53 protein in bronchial epithelium of Iranian "mustard lung" patients. Mil Med. 2007;172(1):70-4.
[42]Medoff BD, Wain JC, Seung E, Jackobek R, Means TK, Ginns LC, et al. CXCR3 and its ligands in a murine model of obliterative bronchiolitis: regulation and function. J Immunol. 2006;176(11):7087-95.
[43]Beytut E. Anthracosis in the lungs and associated lymph nodes in sheep and its potential role in the occurrence of pneumonia. Small Ruminant Res. 2002;46(1),15-21.
[44]Wang Z, Chen YW, Zhang JN, Hu XF, Peng MJ. Pentoxifylline attenuates cigarette smoke-induced overexpression of CXCR3 and IP-10 in mice. Chin Med J. 2012;125(11):1980-5.
[45]Costa C, Rufino R, Traves SL, Lapa E Silva JR, Barnes PJ, Donnelly LE. CXCR3 and CCR5 chemokines in induced sputum from patients with COPD. Chest. 2008;133(1):26-33.
[46]Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE, et al. CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(3 Pt 1):822-6.
[47]Saetta M, Mariani M, Panina-Bordignon P, Turato G, Buonsanti C, Baraldo S, et al. Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;165(10):1404-9.
[2]Momeni AZ, Enshaeih S, Meghdadi M, Amindjavaheri M. Skin manifestations of mustard gas. A clinical study of 535 patients exposed to mustard gas. Arch Dermatol. 1992;128(6):775-80.
[3]Borak J, Sidell FR. Agents of chemical warfare: Sulfur mustard. Ann Emerg Med. 1992;21(3):303-8.
[4]Rowell M, Kehe K, Balszuweit F, Thiermann H. The chronic effects of sulfur mustard exposure. Toxicology. 2009;263(1):9-11.
[5]Razavi SM, Ghanei M, Salamati P, Safiabadi M. Long-term effects of mustard gas on respiratory system of Iranian veterans after Iraq-Iran war: A review. Chin J Traumatol. 2013;16(3):163-8.
[6]Somani SM, Babu SR. Toxicodynamics of sulfur mustard. Int J Clin Pharmacol Ther Toxicol. 1989;27(9):419-35.
[7]Robert JJ, Warwick GP. Studies of mode of action of alkylation against. VI. The metabolism of BIS-2- chloroethylsulphid (mustard gas) and related compounds. Biochem Pharmacol. 1963;12:1329-34.
[8]Malaviya R, Sunil VR, Cervelli J, Anderson DR, Holmes WW, Conti ML, et al. Inflammatory effects of inhaled sulfur mustard in rat lung. Toxicol Appl Pharmacol. 2010;248(2):89-99.
[9]Ghanei M, Harandi AA. Molecular and cellular mechanism of lung injuries due to exposure to sulfur mustard: A review. Inhal Toxicol. 2011;23(7):363-71.
[10]Emad A, Rezaian GhR. The diversity of the effects of sulfur mustard gas inhalation on respiratory system 10 years after a single, heavy exposure analysis of 197 cases. CHEST J. 1997;112(3):734-8.
[11]Myers JL, Colby TV. Pathologic manifestations of bronchiolitis, constrictive bronchiolitis, cryptogenic organizing pneumonia, and diffuse panbronchiolitis. Clin Chest Med. 1993;14(4):611-22.
[12]Taghaddosinejad F, Fayyaz AF, Behnoush B. Pulmonary complications of mustard gas exposure: a study on cadavers. Acta Med Iran. 2011;49(4):233-6.
[13]Mishra NC, Rir-sima-ah J, Grotendorst GR, Langley RJ, Singh SP, Gundavarapu S, et al. Inhalation of sulfur mustard causes long-term T cell-dependent inflammation: possible role of Th17 cells in chronic lung pathology. Int Immunopharmacol. 2012;13(1):101-8.
[14]Weinberger B, Laskin JD, Sunil VR, Sinko PJ, Heck DE, Laskin DL. Sulfur mustard-induced pulmonary injury: therapeutic approaches to mitigating toxicity. Pulm Pharmacol Ther. 2011;24(1):92-9.
[15]Comerford I, McColl SR. Mini-review series: Focus on chemokines. Immunol Cell Biol. 2011 Feb;89(2):183-4.
[16]Griffith JW, Sokol CL, Luster AD. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu Rev Immunol. 2014;32:659-702.
[17]Balestrieri ML, Balestrieri A, Mancini FP, Napoli C. Understanding the immunoangiostatic CXC chemokine network. Cardiovasc Res. 2008;78(2):250-6.
[18]Belperio JA, Keane MP, Arenberg DA, Addison CL, Ehlert JE, Burdick MD, et al. CXC chemokines in angiogenesis. J Leukoc Biol. 2000;68(1):1-8.
[19]Cyster JG. Chemokines and cell migration in secondary lymphoid organs. Science. 1999;286(5447):2098-102.
[20]Strieter RM, Gomperts BN, Keane MP. The role of CXC chemokines in pulmonary fibrosis. J Clin Invest. 2007;117(3):549-56.
[21]Holloway RA, Donnelly LE. Immunopathogenesis of chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2013;19(2):95-102.
[22]MacNee W. Pathogenesis of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(4):258-66.
[23]Chen H, Wang D, Wang X. Role of airway epithelium-origin chemokines and their receptors in COPD. J Epithel Biol Pharmacol. 2010;3:26-33.
[24]Jin T, Xu X, Hereld D. Chemotaxis, chemokine receptors and human disease. Cytokine. 2008;44(1):1-8.
[25]Keane MP. The role of chemokines and cytokines in lung fibrosis. Eur Resir Rev. 2008;17(109):151-6.
[26]Dong S, Zhang X, He Y, Xu F, Li D, Xu W, et al. Synergy of IL-27 and TNF-α in regulating CXCL10 expression in lung fibroblasts. Am J Respir Cell Mol Biol. 2013;48(4):518-30.
[27]Jiang D, Liang J, Hodge J, Lu B, Zhu Z, Yu S, et al. Regulation of pulmonary fibrosis by chemokine receptor CXCR3. J Clin Invest. 2004;114(2):291-9.
[28]Burdick MD, Murray LA, Keane MP, Xue YY, Zisman DA, Belperio JA, et al. CXCL11 attenuates bleomycin-induced pulmonary fibrosis via inhibition of vascular remodeling. Am J Respir Crit Care Med. 2005;171(3):261-8.
[29]Tager AM, Kradin RL, LaCamera P, Bercury SD, Campanella GS, Leary CP, et al. Inhibition of pulmonary fibrosis by chemokin IP10/CXCL10. Am J Respir Cell Mol Biol. 2004;31(4):395-404.
[30]Jiang D, Liang J, Guo R, Xie T, Kelly FL, Martinu T, et al. Long-term exposure of chemokine CXCL10 causes bronchiolitis-like inflammation. Am J Respir Cell Mol Biol. 2012;46(5):592-8.
[31]Agostini C, Calabrese F, Poletti V, Marcer G, Facco M, Miorin M, et al. CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis. Respir Res. 2005;22;6:20.
[32]Ghazanfari T, Yaraee R, Kariminia A, Ebtekar M, Faghihzadeh S, Vaez-Mahdavi MR, et al. Alterations in the serum levels of chemokines 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1471-6.
[33]Yaraee R, Ghazanfari T, Ebtekar M, Ardestani SK, Rezaei A, Kariminia A, et al. Alterations in serum levels of inflammatory cytokines (TNF, IL-1alpha, IL-1beta and IL-1Ra) 20 years after sulfur mustard exposure: Sardasht-Iran cohort study. Int Immunopharmacol. 2009;9(13-14):1466-70.
[34]Yaraee R, Ghazanfari T, Faghihzadeh S, Mostafaie A, Soroush MR, Inai K, et al. Alterations in the serum levels of soluble L, P and E-selectin 20 years after sulfur mustard exposure: Sardasht-Iran Cohort Study. Int Immunopharmacol. 2009;9(13-14):1477-81.
[35]Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-8.
[36]Ghanei M, Adibi I. Clinical review of mustard lung. Iran J Med Sci. 2007;32(2):58-65.
[37]Lari SM, Attaran D, Towhidi M. COPD Due to Sulfur Mustard (Mustard Lung). In: Ong KCh. Chronic Obstructive Pulmonary Disease - Current Concepts and Practice. Croatia: InTech; 2012. Pp. 231-238.
[38]Attaran D, Lari SM, Khajehdaluee M, Ayatollahi H, Towhidi M, Asnaashari A, et al. Highly sensitive C-reactive protein levels in Iranian patients with pulmonary complication of sulfur mustard poisoning and its correlation with severity of airway diseases. Hum Exp Toxicol. 2009;28(12):739-45.
[39]Attaran D, Lari SM, Towhidi M, Marallu HG, Ayatollahi H, Khajehdaluee M, et al. Interleukin-6 and airflow limitation in chemical warfare patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2010;5:335-40
[40]Pourfarzam S, Ghazanfari T, Merasizadeh J, Ghanei M, Azimi G, Araghizadeh H, et al. Long-term pulmonary complications in sulfur mustard victims of Sardasht, Iran. Toxin Rev. 2009;28(1):8-13.
[41]Ghanei M, Amiri S, Akbari H, Kosari F, Khalili AR, Alaeddini F, et al. Correlation of sulfur mustard exposure and tobacco use with expression (immunoreactivity) of p53 protein in bronchial epithelium of Iranian "mustard lung" patients. Mil Med. 2007;172(1):70-4.
[42]Medoff BD, Wain JC, Seung E, Jackobek R, Means TK, Ginns LC, et al. CXCR3 and its ligands in a murine model of obliterative bronchiolitis: regulation and function. J Immunol. 2006;176(11):7087-95.
[43]Beytut E. Anthracosis in the lungs and associated lymph nodes in sheep and its potential role in the occurrence of pneumonia. Small Ruminant Res. 2002;46(1),15-21.
[44]Wang Z, Chen YW, Zhang JN, Hu XF, Peng MJ. Pentoxifylline attenuates cigarette smoke-induced overexpression of CXCR3 and IP-10 in mice. Chin Med J. 2012;125(11):1980-5.
[45]Costa C, Rufino R, Traves SL, Lapa E Silva JR, Barnes PJ, Donnelly LE. CXCR3 and CCR5 chemokines in induced sputum from patients with COPD. Chest. 2008;133(1):26-33.
[46]Saetta M, Di Stefano A, Turato G, Facchini FM, Corbino L, Mapp CE, et al. CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(3 Pt 1):822-6.
[47]Saetta M, Mariani M, Panina-Bordignon P, Turato G, Buonsanti C, Baraldo S, et al. Increased expression of the chemokine receptor CXCR3 and its ligand CXCL10 in peripheral airways of smokers with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2002;165(10):1404-9.