Iranian Journal of Allergy, Asthma and Immunology 2017. 16(5):418-424.

Macrophages from Behcet's Disease Patients Express Decreased Level of Aryl Hydrocarbon Receptor (AHR) mRNA
Mohammad Taghi Palizgir, Maryam Akhtari, Mahdi Mahmoudi, Shayan Mostafaei, Alireza Rezaeimanesh, Massoomeh Akhlaghi, Farhad Shahram

Abstract


Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, connecting environmental stimulators with the immune system. M1 macrophages are a part of immune system that contribute to the inflammatory events in the pathogenesis of Behcet's disease (BD). The effect of AHR on the macrophages in BD patients is still unclear. In this study, we investigated the mRNA expression of AHR in the monocyte-derived and M1 macrophages in active BD patients in comparison to healthy controls. Isolated monocytes from 10 healthy controls and 10 active BD patients were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days. Cells were then polarized to M1 macrophages by lipopolysaccharide (LPS) and interferon-γ (IFNγ) for 24h. Monocyte purity and macrophage markers expression were analyzed by flow cytometry. Analysis of AHR mRNA expression was performed by SYBR Green real-time PCR. Our results showed that AHR expression is significantly down-regulated in M1 macrophages compare to monocyte-derived macrophages. It was shown that both monocyte-derived macrophages and M1 macrophages from BD patients significantly express lower level of AHR mRNA compared to healthy individuals. Our results demonstrate an anti-inflammatory role for AHR in macrophages, which suggest that decreased AHR expression is associated with pro-inflammatory M1 macrophage and BD susceptibility.


Keywords


Aryl hydrocarbon receptor; Behcet's disease; Gene expression

Full Text:

PDF

References


style='font-size:12.0pt;mso-bidi-font-family:"B Yagut";color:#231F20'>

style='mso-element:field-begin'>

color:#231F20'> ADDIN EN.REFLIST

style='font-size:12.0pt;mso-bidi-font-family:"B Yagut";color:#231F20'>

style='mso-element:field-separator'>1.         Mazzoccoli G, Matarangolo A, Rubino R, Inglese M, De Cata A. Behcet syndrome: from pathogenesis to novel therapies. Clinical and experimental medicine. 2016;16(1):1-12.

2.         Mat MC, Sevim A, Fresko I, Tuzun Y. Behcet's disease as a systemic disease. Clinics in dermatology. 2014;32(3):435-42.

3.         Davatchi F, Jamshidi AR, Banihashemi AT, Gholami J, Forouzanfar MH, Akhlaghi M, et al. WHO-ILAR COPCORD Study (Stage 1, Urban Study) in Iran. The Journal of rheumatology. 2008;35(7):1384.

4.         Palizgir M, Mahmoudi M, Qorbani M, Djalalinia S, Mostafaei S, Shahram F. Prevalence and Clinical Investigation of the Behcet’s Disease in Middle East and North Africa: A Systematic Review and Meta-Analysis. Iran Red Crescent Med J.In press(In press):e43313.

5.         Laria A, Lurati A, Marrazza M, Mazzocchi D, Re KA, Scarpellini M. The macrophages in rheumatic diseases. Journal of inflammation research. 2016;9:1-11.

6.         Gul A. Pathogenesis of Behcet's disease: autoinflammatory features and beyond. Seminars in immunopathology. 2015;37(4):413-8.

7.         Mohammadi-Bardbori A, Bengtsson J, Rannug U, Rannug A, Wincent E. Quercetin, resveratrol, and curcumin are indirect activators of the aryl hydrocarbon receptor (AHR). Chemical research in toxicology. 2012;25(9):1878-84.

8.         Stockinger B, Di Meglio P, Gialitakis M, Duarte JH. The aryl hydrocarbon receptor: multitasking in the immune system. Annual review of immunology. 2014;32:403-32.

9.         Nguyen NT, Nakahama T, Nguyen CH, Tran TT, Le VS, Chu HH, et al. Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis. Journal of experimental pharmacology. 2015;7:29-35.

10.       Busbee PB, Rouse M, Nagarkatti M, Nagarkatti PS. Use of natural AhR ligands as potential therapeutic modalities against inflammatory disorders. Nutrition reviews. 2013;71(6):353-69.

11.       Nguyen NT, Hanieh H, Nakahama T, Kishimoto T. The roles of aryl hydrocarbon receptor in immune responses. International immunology. 2013;25(6):335-43.

12.       Kerkvliet NI, Steppan LB, Vorachek W, Oda S, Farrer D, Wong CP, et al. Activation of aryl hydrocarbon receptor by TCDD prevents diabetes in NOD mice and increases Foxp3+ T cells in pancreatic lymph nodes. Immunotherapy. 2009;1(4):539-47.

13.       Marshall NB, Vorachek WR, Steppan LB, Mourich DV, Kerkvliet NI. Functional characterization and gene expression analysis of CD4+ CD25+ regulatory T cells generated in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Journal of immunology. 2008;181(4):2382-91.

14.       Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, et al. Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature. 2008;453(7191):65-71.

15.       Criteria for diagnosis of Behcet's disease. International Study Group for Behcet's Disease. Lancet. 1990;335(8697):1078-80.

16.       Rezaiemanesh A, Mahmoudi M, Amirzargar AA, Vojdanian M, Jamshidi AR, Nicknam MH. Ankylosing spondylitis M-CSF-derived macrophages are undergoing unfolded protein response (UPR) and express higher levels of interleukin-23. Modern rheumatology. 2016:1-6.

17.       Schmittgen TD, Livak KJ. Analyzing real-time PCR data by the comparative C(T) method. Nature protocols. 2008;3(6):1101-8.

18.       Gholijani N, Ataollahi MR, Samiei A, Aflaki E, Shenavandeh S, EskandarKamali S. An elevated pro-inflammatory cytokines profile in Behcet's disease: A multiplex analysis. Immunology letters. 2016.

19.       Misumi M, Hagiwara E, Takeno M, Takeda Y, Inoue Y, Tsuji T, et al. Cytokine production profile in patients with Behcet's disease treated with infliximab. Cytokine. 2003;24(5):210-8.

20.       Jou IM, Lin CF, Tsai KJ, Wei SJ. Macrophage-mediated inflammatory disorders. Mediators of inflammation. 2013;2013:316482.

21.       Zhu C, Xie Q, Zhao B. The role of AhR in autoimmune regulation and its potential as a therapeutic target against CD4 T cell mediated inflammatory disorder. International journal of molecular sciences. 2014;15(6):10116-35.

22.       Kimura A, Naka T, Nakahama T, Chinen I, Masuda K, Nohara K, et al. Aryl hydrocarbon receptor in combination with Stat1 regulates LPS-induced inflammatory responses. The Journal of experimental medicine. 2009;206(9):2027-35.

23.       Sekine H, Mimura J, Oshima M, Okawa H, Kanno J, Igarashi K, et al. Hypersensitivity of aryl hydrocarbon receptor-deficient mice to lipopolysaccharide-induced septic shock. Molecular and cellular biology. 2009;29(24):6391-400.

24.       Climaco-Arvizu S, Dominguez-Acosta O, Cabanas-Cortes MA, Rodriguez-Sosa M, Gonzalez FJ, Vega L, et al. Aryl hydrocarbon receptor influences nitric oxide and arginine production and alters M1/M2 macrophage polarization. Life sciences. 2016;155:76-84.

25.       Wang C, Ye Z, Kijlstra A, Zhou Y, Yang P. Decreased expression of the aryl hydrocarbon receptor in ocular Behcet's disease. Mediators of inflammation. 2014;2014:195094.

26.       Harel-Meir M, Sherer Y, Shoenfeld Y. Tobacco smoking and autoimmune rheumatic diseases. Nature clinical practice Rheumatology. 2007;3(12):707-15.

27.       Klareskog L, Padyukov L, Alfredsson L. Smoking as a trigger for inflammatory rheumatic diseases. Current opinion in rheumatology. 2007;19(1):49-54.

28.       Shamsian E, Azarian M, Akhlaghi M, Samaei M, Jamshidi AR, Assar S, et al. PADI4 Polymorphisms in Iranian Patients with Rheumatoid Arthritis. Acta reumatologica portuguesa. 2016;41(4):338-43.

29.       Fallahi S, Jamshidi AR, Gharibdoost F, Mahmoudi M, Ahmadzadeh N, Nicknam MH. The correlation between pack-years of smoking and disease activity, quality of life, spinal mobility, and sacroiliitis grading in patients with ankylosing spondylitis. Turk J Rheumatol. 2013;28(3):181-8.

30.       Denison MS, Phelan D, Winter GM, Ziccardi MH. Carbaryl, a carbamate insecticide, is a ligand for the hepatic Ah (dioxin) receptor. Toxicology and applied pharmacology. 1998;152(2):406-14.

31.       Baglole CJ, Maggirwar SB, Gasiewicz TA, Thatcher TH, Phipps RP, Sime PJ. The aryl hydrocarbon receptor attenuates tobacco smoke-induced cyclooxygenase-2 and prostaglandin production in lung fibroblasts through regulation of the NF-kappaB family member RelB. The Journal of biological chemistry. 2008;283(43):28944-57.

32.       Soy M, Erken E, Konca K, Ozbek S. Smoking and Behcet's disease. Clinical rheumatology. 2000;19(6):508-9.

font-family:"Times New Roman",serif;mso-fareast-font-family:Calibri;color:#231F20;

mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:AR-SA'>

style='mso-element:field-end'>


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.