Iranian Journal of Allergy, Asthma and Immunology 2017. 16(5):396-403.

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
Parisa Farahani, Raheleh Halabian, Ensieh Vahedi, Jafar Salimian

Abstract


The long lasting inflammation and immune dysregulation is one of the main mechanisms involved in lung complication of veterans exposed to sulfur mustard (SM) gas. Th17/Treg cells have an important role in immunopathogenesis of chronic obstructive pulmonary disease (COPD) and mustard lung disease. In this study, expression of cytokines genes levels related to Th17/Treg cells was determined in peripheral blood mononuclear (PBMC) of mustard lung patients and was compared with COPD patients and healthy controls (HC). Real time-polymerase chain reaction was used to assay genes expression levels of Th17 related cytokines (IL-17, IL-6 and TGF-β) and Treg related cytokines (IL-10, TGF-β). IL-17 gene expression level considerably was higher in SM patients (9.98±0.65, p<0.001), and COPD (4.75±0.71, p<0.001), compare to HC group. Also, gene expression level of IL-6 in the SM group (3.31±0.93, p<0.001) and COPD group (2.93±0.21, p<0.001) were significantly higher than the HC group. The IL-10 gene expression level showed a high increase in SM patients (4.12±0.91, p<0.01), and COPD (2.1±0.45, p<0.01). Finally, the TGF-β gene expression level was increased in SM patients (4.91±0.69, p<0.001) as well as in COPD group (5.41±0.78, p<0.001). In SM patients, IL-17 (R=-0.721, p<0.05), IL-6 (R=-0.621, p<0.05) and TGF-β (R=-0.658, p<0.05) had significant negative association with FEV1 (%). Inversely, Il-10 showed positive correlation (R=0.673) with FEV1 (%). Th17/Treg cells related cytokines genes were highly expressed and imbalanced in peripheral blood mononuclear cells of SM and COPD patients which correlated with pulmonary dysfunction.


Keywords


Chronic obstructive pulmonary disease (COPD); Gene expression; Mustard lung patients; Peripheral blood mononuclear cell (PBMC); Th17/Treg related cytokines

Full Text:

PDF

References


1.            Sahebkar A, Antonelli-Incalzi R, Panahi Y, Ghanei M, Pedone C. Mustard lung and COPD: common features and treatment? The Lancet Respiratory Medicine. 2015;3(10):747-8.

2.            Najafi A, Ghanei M, Jamalkandi SA. Airway remodeling: Systems biology approach, from bench to bedside. Technology and Health Care. 2016(Preprint):1-9.

3.            Tahmasbpour E, Ghanei M, Qazvini A, Vahedi E, Panahi Y. Gene expression profile of oxidative stress and antioxidant defense in lung tissue of patients exposed to sulfur mustard. Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 2016;800:12-21.

4.            Tahmasbpour Marzony E, Ghanei M, Panahi Y. Oxidative stress and altered expression of peroxiredoxin genes family (PRDXS) and sulfiredoxin-1 (SRXN1) in human lung tissue following exposure to sulfur mustard. Experimental lung research. 2016:1-10.

5.            Tahmasbpour E, Reza Emami S, Ghanei M, Panahi Y. Role of oxidative stress in sulfur mustard-induced pulmonary injury and antioxidant protection. Inhalation toxicology. 2015;27(13):659-72.

6.            Bhat TA, Panzica L, Kalathil SG, Thanavala Y. Immune dysfunction in patients with chronic obstructive pulmonary disease. Annals of the American Thoracic Society. 2015;12(Supplement 2):S169-S75.

7.            Ghanei M, Harandi AA. Mustard Lung: Diagnosis and Treatment of Respiratory Disorders in Sulfur-Mustard Injured Patients: Academic Press; 2016.

8.            Mahmoudi M, Hefazi M, Rastin M, Balali-Mood M. Long-term hematological and immunological complications of sulfur mustard poisoning in Iranian veterans. International immunopharmacology. 2005;5(9):1479-85.

9.            Ghazanfari T, Kariminia A, Yaraee R, Faghihzadeh S, Ardestani SK, Ebtekar M, et al. Long term impact of sulfur mustard exposure on peripheral blood mononuclear subpopulations—Sardasht-Iran Cohort Study (SICS). International immunopharmacology. 2013;17(3):931-5.

10.          Ghasemi H, Ghazanfari T, Yaraee R, Pourfarzam S, Soroush M-R, Faghihzadeh S, et al. Evaluation of the tear and serum levels of IL-8 in sulfur mustard intoxicated patients 20 years after exposure. Cutaneous and ocular toxicology. 2012;31(2):132-7.

11.          Isailovic N, Daigo K, Mantovani A, Selmi C. Interleukin-17 and innate immunity in infections and chronic inflammation. Journal of autoimmunity. 2015;60:1-11.

12.          Mease PJ. Inhibition of interleukin-17, interleukin-23 and the TH17 cell pathway in the treatment of psoriatic arthritis and psoriasis. Current opinion in rheumatology. 2015;27(2):127-33.

13.          Ziegler SF, Buckner JH. FOXP3 and the regulation of Treg/Th17 differentiation. Microbes and Infection. 2009;11(5):594-8.

14.          Fatemi K, Radvar M, Rezaee A, Rafatpanah H, Dadpour Y, Radvar N. Comparison of relative TLR‐2 and TLR‐4 expression level of disease and healthy gingival tissue of smoking and non‐smoking patients and periodontally healthy control patients. Australian dental journal. 2013;58(3):315-20.

15.          Buckley CD, Barone F, Nayar S, Benezech C, Caamano J. Stromal cells in chronic inflammation and tertiary lymphoid organ formation. Annual review of immunology. 2015;33:715-45.

16.          Song X, Gao H, Qian Y. Th17 differentiation and their pro-inflammation function.  T Helper Cell Differentiation and Their Function: Springer; 2014. p. 99-151.

17.          Bao Y, Cao X. The immune potential and immunopathology of cytokine-producing B cell subsets: a comprehensive review. Journal of autoimmunity. 2014;55:10-23.

18.          Shohrati M, Amini-Harandi A, Najafian B, Saburi A, Ghanei M. The role of serum level of interleukin-6 in severity of pulmonary complications of sulfur mustard injuries. Iranian journal of medical sciences. 2014;39(4):382.

19.          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. Journal of Receptors and Signal Transduction. 2016:1-11.

20.          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. Immunopharmacology and immunotoxicology. 2016:1-11.

21.          Roudkenar MH, Halabian R, Oodi A, Roushandeh AM, Yaghmai P, Najar MR, Amirizadeh N, Shokrgozar MA. Upregulation of neutrophil gelatinase-associated lipocalin, NGAL/Lcn2, in beta-thalassemia patients. Arch Med Res 2008;39(4):402-7.

22.          Andersen LB, Jørgensen JS, Jensen TK, Dalgård C, Barington T, Nielsen J, et al. Vitamin D insufficiency is associated with increased risk of first-trimester miscarriage in the Odense Child Cohort. The American journal of clinical nutrition. 2015;102(3):633-8.

23.          Panahi Y, Jadidi-Niaragh F, Azimzadeh Jamalkandi S, Ghanei M, Pedone C, Nikravanfard N, et al. Immunology of Chronic Obstructive Pulmonary Disease and Sulfur Mustard Induced Airway Injuries: Implications for Immunotherapeutic Interventions. Current pharmaceutical design. 2016;22(20):2975-96.

24.          Razavi SM, Negahban Z, Pirhosseinloo M, Razavi MS, Hadjati G, Salamati P. Sulfur mustard effects on mental health and quality-of-life: a review. Iranian journal of psychiatry and behavioral sciences. 2014;8(3):11.

25.          Vargas-Rojas MI, Ramírez-Venegas A, Limón-Camacho L, Ochoa L, Hernández-Zenteno R, Sansores RH. Increase of Th17 cells in peripheral blood of patients with chronic obstructive pulmonary disease. Respiratory medicine. 2011;105(11):1648-54.

26.          Di Stefano A, Caramori G, Gnemmi I, Contoli M, Vicari C, Capelli A, et al. T helper type 17‐related cytokine expression is increased in the bronchial mucosa of stable chronic obstructive pulmonary disease patients. Clinical & Experimental Immunology. 2009;157(2):316-24.

27.          Pridgeon C, Bugeon L, Donnelly L, Straschil U, Tudhope SJ, Fenwick P, et al. Regulation of IL-17 in chronic inflammation in the human lung. Clinical science. 2011;120(12):515-24.

28.          Wang H, Ying H, Wang S, Gu X, Weng Y, Peng W, et al. Imbalance of peripheral blood Th17 and Treg responses in patients with chronic obstructive pulmonary disease. The clinical respiratory journal. 2015;9(3):330-41.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.