Is the Inflammasome Pathway Active in the Peripheral Blood of Sulfur Mustard-exposed Patients?
-
Sholeh Etehad Asnaf
,
Mitra Sabetghadam
,
Habib Jaafarinejad
,
Raheleh Halabian
,
Shahram Parvin
,
Ensieh Vahedi
,
Nasrin Pazoki
,
Jafar Salimian
Abstract
The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1β, IL-18, and IL-1βR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients.
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2. Ghanei M, Mokhtari M, Mohammad MM, Aslani J. Bronchiolitis obliterans following exposure to sulfur mustard: chest high resolution computed tomography. Eur J Radiol 2004;52(2):164-9.
3. Sun M, Yang Y, Meng W, Xu Q, Lin F, Chen Y, et al. Advanced biotherapy for the treatment of sulfur mustard poisoning. Chem Biol Interact 2018; 111-118.
4. Imani S, Panahi Y, Salimian J, Fu J, Ghanei M. Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study. Iran J Basic Med Sci 2015;18(8):723.
5. Behboudi H, Noureini SK, Ghazanfari T, Ardestani SK. DNA damage and telomere length shortening in the peripheral blood leukocytes of 20 years SM-exposed veterans. Int Immunopharmacol 2018;61:37-44.
6. Simons T, Steinritz D, Bölck B, Schmidt A, Popp T, Thiermann H, et al. Sulfur mustard-induced epigenetic modifications over time− a pilot study. Toxicol Lett 2018;293:45-50.
7. Shahriary A, Seyedzadeh MH, Ahmadi A, Salimian J. The footprint of TGF-β in airway remodeling of the mustard lung. Inhal Toxicol 2015;27(14):745-53.
8. Imani S, Salimian J, Bozorgmehr M, Vahedi E, Ghazvini A, Ghanei M, et al. Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease. J Recept Signal Transduct Res 2016;36(5):531-41.
9. Imani S, Salimian J, Fu J, Ghanei M, Panahi Y. Th17/Treg-related cytokine imbalance in sulfur mustard exposed and stable chronic obstructive pulmonary (COPD) patients: correlation with disease activity. Immunopharmacol Immunotoxicol 2016;38(4):270-80.
10. Iman M, Rezaei R, Azimzadeh Jamalkandi S, Shariati P, et al Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases. Expert Rev Clin Immuno 2017;13(12):1173-88.
11. Saeedi P, Salimian J, Ahmadi A, Imani Fooladi AA. The transient but not resident (TBNR) microbiome: a Yin Yang model for lung immune system. Inhal Toxicol 2015;27(10):451-61.
12. Di Stefano A, Caramori G, Barczyk A, Vicari C, Brun P, Zanini A, et al. Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD. Thorax 2014; 69(6):519-24.
13. Scambler T, Holbrook J, Savic S, McDermott MF, Peckham D. Autoinflammatory disease in the lung. Immunology 2018.
14. Ather JL, Martin RA, Ckless K, Poynter ME. Inflammasome activity in non-microbial lung inflammation. J Environ Immunol Toxicol 2014;1(3):108.
15. Brusselle GG, Provoost S, Bracke KR, Kuchmiy A, Lamkanfi M. Inflammasomes in respiratory disease: from bench to bedside. Chest 2014;145(5):1121-33.
16. Boraschi D, Lucchesi D, Hainzl S, Leitner M, Maier E, Mangelberger D, et al. IL-37: a new anti-inflammatory cytokine of the IL-1 family. Eur Cytokine Netw 2011;22(3):127-47.
17. Tete S, Tripodi D, Rosati M, Conti F, Maccauro G, Saggini A, et al. IL-37 (IL-1F7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation. SAGE Publications Sage UK: London, England; 2012.
18. Ghanei M, Harandi AA. Long term consequences from exposure to sulfur mustard: a review. Inhal Toxicol 2007;19(5):451-6.
19. 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.
20. Shohrati M, Ghanei M, Shamspour N, Jafari M. Activity and function in lung injuries due to sulphur mustard. Biomarkers 2008;13(7-8):728-33.
21. Eghtedardoost M, Hassan ZM, Ghazanfari T, Sadeghipour A, Ghanei M. Evaluation of mRNA Expression Levels of TNFα, TNFR1 and IL1β in Lung Tissue 20 Years after Sulfur-mustard Exposure. Iran J Allergy Asthma Immunol 2018;17(4):379-87.
22. Eltom S, Belvisi MG, Stevenson CS, Maher SA, Dubuis E, Fitzgerald KA, et al. Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation: an insight into the pathogenesis of COPD. PloS one 2014;9(11):e112829.
23. Faner R, Sobradillo P, Noguera A, Gomez C, Cruz T, López-Giraldo A, et al. The inflammasome pathway in stable COPD and acute exacerbations. ERJ Open Res 2016;2(3):00002-2016.
24. Levandowski CB, Mailloux CM, Ferrara TM, Gowan K, Ben S, Jin Y, et al. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. Proc Natl Acad Sci U S A 2013;110(8):2952-6.
25. Nold-Petry CA, Lo CY, Rudloff I, Elgass KD, Li S, Gantier MP, et al. IL-37 requires the receptors IL-18Rα and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol 2015;16(4):354-65.
26. Emad A, Emad Y. Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis. Respir Med 2007;101(4):786-92.
27. Farahani P, Halabian R, Vahedi E, Salimian J. Increased Genes Expression Levels of Cytokines Related to Th17/Treg Cells in Peripheral Blood Mononuclear Cell Correlate with Clinical Severity in COPD and Mustard Gas-exposed Patients. Iran J Allergy Asthma Immunol 2017;16(5):396-403.
28. Dinarello CA, Nold‐Petry C, Nold M, Fujita M, Li S, Kim S, et al. Suppression of innate inflammation and immunity by interleukin‐37. Eur J Immunol 2016;46(5):1067-81.
29. Bulau A-M, Nold MF, Li S, Nold-Petry CA, Fink M, Mansell A, et al. Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses. Proc Natl Acad Sci U S A 2014;111(7):2650-5.
2. Ghanei M, Mokhtari M, Mohammad MM, Aslani J. Bronchiolitis obliterans following exposure to sulfur mustard: chest high resolution computed tomography. Eur J Radiol 2004;52(2):164-9.
3. Sun M, Yang Y, Meng W, Xu Q, Lin F, Chen Y, et al. Advanced biotherapy for the treatment of sulfur mustard poisoning. Chem Biol Interact 2018; 111-118.
4. Imani S, Panahi Y, Salimian J, Fu J, Ghanei M. Epigenetic: A missing paradigm in cellular and molecular pathways of sulfur mustard lung: a prospective and comparative study. Iran J Basic Med Sci 2015;18(8):723.
5. Behboudi H, Noureini SK, Ghazanfari T, Ardestani SK. DNA damage and telomere length shortening in the peripheral blood leukocytes of 20 years SM-exposed veterans. Int Immunopharmacol 2018;61:37-44.
6. Simons T, Steinritz D, Bölck B, Schmidt A, Popp T, Thiermann H, et al. Sulfur mustard-induced epigenetic modifications over time− a pilot study. Toxicol Lett 2018;293:45-50.
7. Shahriary A, Seyedzadeh MH, Ahmadi A, Salimian J. The footprint of TGF-β in airway remodeling of the mustard lung. Inhal Toxicol 2015;27(14):745-53.
8. Imani S, Salimian J, Bozorgmehr M, Vahedi E, Ghazvini A, Ghanei M, et al. Assessment of Treg/Th17 axis role in immunopathogenesis of chronic injuries of mustard lung disease. J Recept Signal Transduct Res 2016;36(5):531-41.
9. Imani S, Salimian J, Fu J, Ghanei M, Panahi Y. Th17/Treg-related cytokine imbalance in sulfur mustard exposed and stable chronic obstructive pulmonary (COPD) patients: correlation with disease activity. Immunopharmacol Immunotoxicol 2016;38(4):270-80.
10. Iman M, Rezaei R, Azimzadeh Jamalkandi S, Shariati P, et al Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases. Expert Rev Clin Immuno 2017;13(12):1173-88.
11. Saeedi P, Salimian J, Ahmadi A, Imani Fooladi AA. The transient but not resident (TBNR) microbiome: a Yin Yang model for lung immune system. Inhal Toxicol 2015;27(10):451-61.
12. Di Stefano A, Caramori G, Barczyk A, Vicari C, Brun P, Zanini A, et al. Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD. Thorax 2014; 69(6):519-24.
13. Scambler T, Holbrook J, Savic S, McDermott MF, Peckham D. Autoinflammatory disease in the lung. Immunology 2018.
14. Ather JL, Martin RA, Ckless K, Poynter ME. Inflammasome activity in non-microbial lung inflammation. J Environ Immunol Toxicol 2014;1(3):108.
15. Brusselle GG, Provoost S, Bracke KR, Kuchmiy A, Lamkanfi M. Inflammasomes in respiratory disease: from bench to bedside. Chest 2014;145(5):1121-33.
16. Boraschi D, Lucchesi D, Hainzl S, Leitner M, Maier E, Mangelberger D, et al. IL-37: a new anti-inflammatory cytokine of the IL-1 family. Eur Cytokine Netw 2011;22(3):127-47.
17. Tete S, Tripodi D, Rosati M, Conti F, Maccauro G, Saggini A, et al. IL-37 (IL-1F7) the newest anti-inflammatory cytokine which suppresses immune responses and inflammation. SAGE Publications Sage UK: London, England; 2012.
18. Ghanei M, Harandi AA. Long term consequences from exposure to sulfur mustard: a review. Inhal Toxicol 2007;19(5):451-6.
19. 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.
20. Shohrati M, Ghanei M, Shamspour N, Jafari M. Activity and function in lung injuries due to sulphur mustard. Biomarkers 2008;13(7-8):728-33.
21. Eghtedardoost M, Hassan ZM, Ghazanfari T, Sadeghipour A, Ghanei M. Evaluation of mRNA Expression Levels of TNFα, TNFR1 and IL1β in Lung Tissue 20 Years after Sulfur-mustard Exposure. Iran J Allergy Asthma Immunol 2018;17(4):379-87.
22. Eltom S, Belvisi MG, Stevenson CS, Maher SA, Dubuis E, Fitzgerald KA, et al. Role of the inflammasome-caspase1/11-IL-1/18 axis in cigarette smoke driven airway inflammation: an insight into the pathogenesis of COPD. PloS one 2014;9(11):e112829.
23. Faner R, Sobradillo P, Noguera A, Gomez C, Cruz T, López-Giraldo A, et al. The inflammasome pathway in stable COPD and acute exacerbations. ERJ Open Res 2016;2(3):00002-2016.
24. Levandowski CB, Mailloux CM, Ferrara TM, Gowan K, Ben S, Jin Y, et al. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. Proc Natl Acad Sci U S A 2013;110(8):2952-6.
25. Nold-Petry CA, Lo CY, Rudloff I, Elgass KD, Li S, Gantier MP, et al. IL-37 requires the receptors IL-18Rα and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol 2015;16(4):354-65.
26. Emad A, Emad Y. Increased in CD8 T lymphocytes in the BAL fluid of patients with sulfur mustard gas-induced pulmonary fibrosis. Respir Med 2007;101(4):786-92.
27. Farahani P, Halabian R, Vahedi E, Salimian J. Increased Genes Expression Levels of Cytokines Related to Th17/Treg Cells in Peripheral Blood Mononuclear Cell Correlate with Clinical Severity in COPD and Mustard Gas-exposed Patients. Iran J Allergy Asthma Immunol 2017;16(5):396-403.
28. Dinarello CA, Nold‐Petry C, Nold M, Fujita M, Li S, Kim S, et al. Suppression of innate inflammation and immunity by interleukin‐37. Eur J Immunol 2016;46(5):1067-81.
29. Bulau A-M, Nold MF, Li S, Nold-Petry CA, Fink M, Mansell A, et al. Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses. Proc Natl Acad Sci U S A 2014;111(7):2650-5.
| Files | ||
| Issue | Vol 18, No 2 (2019) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v18i2.925 | |
| Keywords | ||
| Chronic obstructive pulmonary disease Gene expression Inflammasome Mustard gas | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Etehad Asnaf S, Sabetghadam M, Jaafarinejad H, Halabian R, Parvin S, Vahedi E, Pazoki N, Salimian J. Is the Inflammasome Pathway Active in the Peripheral Blood of Sulfur Mustard-exposed Patients?. Iran J Allergy Asthma Immunol. 2019;18(2):218-224.
