Evaluation of mRNA Expression Levels of TNFα, TNFR1 and IL1β in Lung Tissue 20 Years after Sulfur-mustard Exposure
Despite many years having passed since exposure to sulfur mustard (SM) gas, there are many exposed subjects who are still suffering from delayed pulmonary complications. The levels of pro-inflammatory cytokines in the lung of these subjects have not been investigated in delay phase. In this study, we evaluated mRNA expression of pro-inflammatory cytokines (tumor necrosis factor alpha (TNFα), tumor necrosis factor receptor type 1 (TNFR1), and interleukin 1 beta (IL-1β) ) in lung biopsy of SM-exposed subjects and compared them with control (non-exposed) subjects. We used formalin-fixed, paraffin-embedded (FFPE) tissue for this purpose. Lung FFPE blocks of SM-exposed subjects (30 samples) and a control group (30 samples) were collected from archival pathology department. The total mRNA of FFPE tissues were extracted and the mRNA expression of pro-inflammatory cytokines were determined by quantitative Real Time PCR (RT-qPCR). The obtained results from two groups were compared to each other and non-parametric statistical analyses were carried out on them. Our studies showed that the mRNA expression of TNFα, TNFR1 and IL-1β in lung tissue of SM injured and control people have no significant difference (p-value= 0.159, 0.832 and 0.314 respectivly). TNFR1 showed direct correlation with TNFα (r=0.867, p=0.002) and IL-1β (r= 0.65, p=0.006). The evaluation of mRNA expression in pro-inflammatory cytokines in lung of SM-exposed subjects after 20 years showed that these mediators are similar to those of non-exposed group and there was no acute inflammation in lung of these patients.
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1. Murakami M, Hirano T. The molecular mechanisms of chronic inflammation development. Frontiers in Immunology. 2012;3(323).
2. Moldoveanu B, Otmishi P, Jani P, Walker J, Sarmiento X, Guardiola J, et al. Inflammatory mechanisms in the lung. Journal of inflammation research. 2009;2:1-11.
3. Aaron SD, Angel JB, Lunau M, Wright K, Fex C, Le Saux N, et al. Granulocyte inflammatory markers and airway infection during acute exacerbation of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001;163(2):349-55.
4. Bhowmik A, Seemungal TA, Sapsford RJ, Wedzicha JA. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax. 2000;55(2):114-20.
5. Bradley JR. TNF-mediated inflammatory disease. J Pathol. 2008;214(2):149-60.
6. Sunil VR, Patel-Vayas K, Shen J, Gow AJ, Laskin JD, Laskin DL. Role of TNFR1 in lung injury and altered lung function induced by the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide. Toxicol Appl Pharmacol. 2011;250(3):245-55.
7. Cho HY, Zhang LY, Kleeberger SR. Ozone-induced lung inflammation and hyperreactivity are mediated via tumor necrosis factor-alpha receptors. Am J Physiol Lung Cell Mol Physiol. 2001;280(3):L537-46.
8. Kehe K, Szinicz L. Medical aspects of sulphur mustard poisoning. Toxicology. 2005;214(3):198-209.
9. Balali-Mood M, Mousavi S, Balali-Mood B. Chronic health effects of sulphur mustard exposure with special reference to Iranian veterans. Emerging health threats journal. 2008;1:e7.
10.Ghanei M, Adibi I. Clinical review of mustard lung. Iranian Journal of Medical Sciences. 2007;32(2):58-65.
11.Lari SM, Attaran D, Towhidi M. COPD Due to Sulfur Mustard (Mustard Lung). Chronic Obstructive Pulmonary Disease - Current Concepts and Practice. 2012:231-9.
12.Ghazanfari T, Faghihzadeh S, Aragizadeh H, Soroush MR, Yaraee R, Mohammad Hassan Z, et al. Sardasht-Iran cohort study of chemical warfare victims: design and methods. Archives of Iranian medicine. 2009;12(1):5-14.
13.Pourfarzam S, Yaraee R, Hassan ZM, Yarmohammadi ME, Faghihzadeh S, Soroush MR, et al. Chemokines, MMP-9 and PMN elastase in spontaneous sputum of sulfur mustard exposed civilians: Sardasht-Iran Cohort Study. International immunopharmacology. 2013:968–73.
14.Emad A, Emad V. Elevated levels of MCP-1, MIP-alpha and MIP-1 beta in the bronchoalveolar lavage (BAL) fluid of patients with mustard gas-induced pulmonary fibrosis. Toxicology. 2007;240(1-2):60-9.
15.Poursaleh Z, Harandi AA, Vahedi E, Ghanei M. Treatment for sulfur mustard lung injuries; new therapeutic approaches from acute to chronic phase. Daru. 2012;20(1):27.
16.Weinberger B, Malaviya R, Sunil VR, Venosa A, Heck DE, Laskin JD, et al. Mustard vesicant-induced lung injury: Advances in therapy. Toxicol Appl Pharmacol. 2016;305:1-11.
17.Vernooy JH, Küçükaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, et al. Local and Systemic Inflammation in Patients with Chronic Obstructive Pulmonary Disease. American Journal of Respiratory and Critical Care Medicine. 2002;166(9):1218-24.
18.Khateri S, Ghanei M, Keshavarz S, Soroush M, Haines D. Incidence of lung, eye, and skin lesions as late complications in 34,000 Iranians with wartime exposure to mustard agent. J Occup Environ Med. 2003;45(11):1136-43.
19.Eghtedardoost M, Hassan ZM, Askari N, Sadeghipour A, Naghizadeh MM, Ghafarpour S, et al. The delayed effect of mustard gas on housekeeping gene expression in lung biopsy of chemical injuries Biophysic and Biochemistry Reports. 2017;11: 27-32.
21.Pfaffi MW. A new mathematical model for relative quantification in real time RT-PCR. Nucleic Acids Research 2001;29(9):1-6.
22.Emad A, Emad Y. CD4/CD8 ratio and cytokine levels of the BAL fluid in patients with bronchiectasis caused by sulfur mustard gas inhalation. J Inflamm (Lond). 2007;4:2.
23.Emad A, Emad Y. Levels of cytokine in bronchoalveolar lavage (BAL) fluid in patients with pulmonary fibrosis due to sulfur mustard gas inhalation. Journal of Interferon & Cytokine Research. 2007;27(1):38-43.
24.Yaraee R, Hassan ZM, Pourfarzam S, Rezaei A, Faghihzadeh S, Ebtekar M, et al. Fibrinogen and inflammatory cytokines in spontaneous sputum of sulfur-mustard-exposed civilians--Sardasht-Iran Cohort Study. Int Immunopharmacol. 2013;17(3):968-73.
25.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) 20years after sulfur mustard exposure: Sardasht-Iran cohort study. International immunopharmacology. 2009;9(13):1466-70.
26.Khazdair MR, Boskabady MH, Ghorani V. Respiratory effects of sulfur mustard exposure, similarities and differences with asthma and COPD. Inhalation toxicology. 2015;27(14):731-44.
27.Ghanei M, Harandi AA. Molecular and cellular mechanism of lung injuries due to exposure to sulfur mustard: a review. Inhalation toxicology. 2011;23(7):363-71.
28.Aghanouri R, Ghanei M, Aslani J, Keivani-Amine H, Rastegar F, Karkhane A. Fibrogenic cytokine levels in bronchoalveolar lavage aspirates 15 years after exposure to sulfur mustard. Am J Physiol Lung Cell Mol Physiol. 2004;287(6):L1160-4.
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|Issue||Vol 17, No 4 (2018)|
|Interleukin-1 beta Lung mRNA expression Sulfur mustard Tumor necrosis factor-alpha Tumor necrosis factor receptor type 1|
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