nach oben

Erschienen in:

09.03.2018 | Original Article

Ankylosing spondylitis monocyte-derived macrophages express increased level of A_2A adenosine receptor and decreased level of ectonucleoside triphosphate diphosphohydrolase-1 (CD39), A₁ and A_2B adenosine receptors

verfasst von: Maryam Akhtari, Seyed Jalal Zargar, Mahdi Mahmoudi, Mahdi Vojdanian, Alireza Rezaeimanesh, Ahmadreza Jamshidi

Erschienen in: Clinical Rheumatology | Ausgabe 6/2018

Einloggen, um Zugang zu erhalten

Abstract

Macrophages play an important role in the ankylosing spondylitis (AS) auto-inflammatory responses and fibrocartilage destruction. Adenosine is a key modulator of inflammatory conditions. The various effects of adenosine are mediated by its interaction with adenosine receptors (AR). In this study, we investigated the mRNA expression of A₁, A_2A, A_2B, and A₃ adenosine receptors, ectonucleoside triphosphate diphosphohydrolase-1 (CD39), and ecto-5′-nucleotidase (CD73) in the monocyte-derived macrophages from AS patients in comparison to healthy controls. We also explored the correlation between analyzed gene expression and patients’ clinical manifestations. Whole blood-separated monocytes from 23 healthy controls and 23 active AS patients were stimulated by macrophage colony-stimulating factor (M-CSF) for 7 days and differentiated to macrophages. Monocyte and macrophage markers were analyzed by flow cytometry. Analysis of adenosine receptors (ADORA1، ADORA2A، ADORA2B، ADORA3), CD39 and CD73 gene expression was performed by SYBR green real-time PCR. Our results demonstrated monocyte-derived macrophages from AS patients expressed increased level of A_2AAR and reduced level of A₁, A_2BAR, and CD39 mRNA compared to healthy controls. We found an inverse correlation between A_2AAR mRNA expression and Bath Ankylosing Spondylitis Functional Index (BASFI) score in AS patients. According to our results, altered expression level of adenosine-relying system would be involved in AS macrophage dysfunction and inflammation and correlated with functional status in AS patients.

Nur mit Berechtigung zugänglich

Braun J, Sieper J (2007) Ankylosing spondylitis. Lancet 369:1379–1390. https://doi.org/10.1016/S0140-6736(07)60635-7 CrossRefPubMed

Tam LS, Gu J, Yu D (2010) Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol 6:399–405. https://doi.org/10.1038/nrrheum.2010.79 CrossRefPubMed

Rudwaleit M, Baeten D (2006) Ankylosing spondylitis and bowel disease. Best Pract Res Clin Rheumatol 20:451–471. https://doi.org/10.1016/j.berh.2006.03.010 CrossRefPubMed

Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, Landewe R, van ver Tempel H, Mielants H, Dougados M, van der Heijde D (2003) Assessment of enthesitis in ankylosing spondylitis. Ann Rheum Dis 62:127–132CrossRefPubMedPubMedCentral

Henderson C, Davis JC (2006) Drug insight: anti-tumor-necrosis-factor therapy for ankylosing spondylitis. Nat Clin Pract Rheumatol 2:211–218. https://doi.org/10.1038/ncprheum0157 CrossRefPubMed

Coates LC, Marzo-Ortega H, Bennett AN, Emery P (2010) Anti-TNF therapy in ankylosing spondylitis: insights for the clinician. Ther Adv Musculoskelet Dis 2:37–43. https://doi.org/10.1177/1759720X09359728 CrossRefPubMedPubMedCentral

Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets Inflamm Allergy 4:281–286CrossRefPubMed

Laria A, Lurati A, Marrazza M, Mazzocchi D, Re KA, Scarpellini M (2016) The macrophages in rheumatic diseases. J Inflamm Res 9:1–11. https://doi.org/10.2147/JIR.S82320 PubMedPubMedCentral

Melis L, Elewaut D (2009) Progress in spondylarthritis. Immunopathogenesis of spondyloarthritis: which cells drive disease? Arthritis Res Ther 11:233. https://doi.org/10.1186/ar2722 CrossRefPubMedPubMedCentral

10.

McGonagle D, Marzo-Ortega H, O'Connor P, Gibbon W, Hawkey P, Henshaw K, Emery P (2002) Histological assessment of the early enthesitis lesion in spondyloarthropathy. Ann Rheum Dis 61:534–537CrossRefPubMedPubMedCentral

11.

Baeten D, De Keyser F (2004) The histopathology of spondyloarthropathy. Curr Mol Med 4:1–12CrossRefPubMed

12.

Bollow M, Fischer T, Reisshauer H, Backhaus M, Sieper J, Hamm B, Braun J (2000) Quantitative analyses of sacroiliac biopsies in spondyloarthropathies: T cells and macrophages predominate in early and active sacroiliitis—cellularity correlates with the degree of enhancement detected by magnetic resonance imaging. Ann Rheum Dis 59:135–140CrossRefPubMedPubMedCentral

13.

Hasko G, Cronstein BN (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25:33–39CrossRefPubMed

14.

Cronstein BN, Sitkovsky M (2017) Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol 13:41–51. https://doi.org/10.1038/nrrheum.2016.178 CrossRefPubMed

15.

Hasko G, Pacher P (2012) Regulation of macrophage function by adenosine. Arterioscler Thromb Vasc Biol 32:865–869. https://doi.org/10.1161/ATVBAHA.111.226852 CrossRefPubMedPubMedCentral

16.

Buenestado A, Grassin Delyle S, Arnould I, Besnard F, Naline E, Blouquit-Laye S, Chapelier A, Bellamy JF, Devillier P (2010) The role of adenosine receptors in regulating production of tumour necrosis factor-alpha and chemokines by human lung macrophages. Br J Pharmacol 159:1304–1311. https://doi.org/10.1111/j.1476-5381.2009.00614.x CrossRefPubMedPubMedCentral

17.

Hasko G, Deitch EA, Szabo C, Nemeth ZH, Vizi ES (2002) Adenosine: a potential mediator of immunosuppression in multiple organ failure. Curr Opin Pharmacol 2:440–444CrossRefPubMed

18.

Majumdar S, Aggarwal BB (2003) Adenosine suppresses activation of nuclear factor-kappaB selectively induced by tumor necrosis factor in different cell types. Oncogene 22:1206–1218. https://doi.org/10.1038/sj.onc.1206184 CrossRefPubMed

19.

Hasko G, Linden J, Cronstein B, Pacher P (2008) Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 7:759–770. https://doi.org/10.1038/nrd2638 CrossRefPubMedPubMedCentral

20.

Hasko G, Kuhel DG, Chen JF, Schwarzschild MA, Deitch EA, Mabley JG, Marton A, Szabo C (2000) Adenosine inhibits IL-12 and TNF-[alpha] production via adenosine A2a receptor-dependent and independent mechanisms. FASEB J 14:2065–2074. https://doi.org/10.1096/fj.99-0508com CrossRefPubMed

21.

Kreckler LM, Wan TC, Ge ZD, Auchampach JA (2006) Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A2A and A2B but not the A3 adenosine receptor. J Pharmacol Exp Ther 317:172–180. https://doi.org/10.1124/jpet.105.096016 CrossRefPubMed

22.

Ryzhov S, Zaynagetdinov R, Goldstein AE, Novitskiy SV, Blackburn MR, Biaggioni I, Feoktistov I (2008) Effect of A2B adenosine receptor gene ablation on adenosine-dependent regulation of proinflammatory cytokines. J Pharmacol Exp Ther 324:694–700. https://doi.org/10.1124/jpet.107.131540 CrossRefPubMed

23.

Le Vraux V, Chen YL, Masson I, De Sousa M, Giroud JP, Florentin I, Chauvelot-Moachon L (1993) Inhibition of human monocyte TNF production by adenosine receptor agonists. Life Sci 52:1917–1924CrossRefPubMed

24.

Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-alpha expression by adenosine: role of A3 adenosine receptors. J Immunol 156:3435–3442PubMed

25.

Blackburn MR, Vance CO, Morschl E, Wilson CN (2009) Adenosine receptors and inflammation. Handb Exp Pharmacol:215–269. https://doi.org/10.1007/978-3-540-89615-9_8

26.

Fredholm BB (2007) Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell Death Differ 14:1315–1323. https://doi.org/10.1038/sj.cdd.4402132 CrossRefPubMed

27.

Hasko G, Cronstein B (2013) Regulation of inflammation by adenosine. Front Immunol 4:85. https://doi.org/10.3389/fimmu.2013.00085 CrossRefPubMedPubMedCentral

28.

Yegutkin GG (2008) Nucleotide- and nucleoside-converting ectoenzymes: important modulators of purinergic signalling cascade. Biochim Biophys Acta 1783:673–694. https://doi.org/10.1016/j.bbamcr.2008.01.024 CrossRefPubMed

29.

Jacob F, Perez Novo C, Bachert C, Van Crombruggen K (2013) Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signal 9:285–306. https://doi.org/10.1007/s11302-013-9357-4 CrossRefPubMedPubMedCentral

30.

Antonioli L, Pacher P, Vizi ES, Hasko G (2013) CD39 and CD73 in immunity and inflammation. Trends Mol Med 19:355–367. https://doi.org/10.1016/j.molmed.2013.03.005 CrossRefPubMedPubMedCentral

31.

Cekic C, Linden J (2016) Purinergic regulation of the immune system. Nat Rev Immunol 16:177–192. https://doi.org/10.1038/nri.2016.4 CrossRefPubMed

32.

Ravani A, Vincenzi F, Bortoluzzi A, Padovan M, Pasquini S, Gessi S, Merighi S, Borea PA, Govoni M, Varani K (2017) Role and function of A2A and A(3) adenosine receptors in patients with ankylosing spondylitis, psoriatic arthritis and rheumatoid arthritis. Int J Mol Sci 18. https://doi.org/10.3390/ijms18040697

33.

van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria Arthritis Rheum 27:361–368PubMed

34.

Bortoluzzi A, Vincenzi F, Govoni M, Padovan M, Ravani A, Borea PA, Varani K (2016) A2A adenosine receptor upregulation correlates with disease activity in patients with systemic lupus erythematosus. Arthritis Res Ther 18:192. https://doi.org/10.1186/s13075-016-1089-8 CrossRefPubMedPubMedCentral

35.

Ochaion A, Bar-Yehuda S, Cohen S, Barer F, Patoka R, Amital H, Reitblat T, Reitblat A, Ophir J, Konfino I, Chowers Y, Ben-Horin S, Fishman P (2009) The anti-inflammatory target A(3) adenosine receptor is over-expressed in rheumatoid arthritis, psoriasis and Crohn's disease. Cell Immunol 258:115–122. https://doi.org/10.1016/j.cellimm.2009.03.020 CrossRefPubMed

36.

Varani K, Padovan M, Vincenzi F, Targa M, Trotta F, Govoni M, Borea PA (2011) A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release. Arthritis Res Ther 13:R197. https://doi.org/10.1186/ar3527 CrossRefPubMedPubMedCentral

37.

Mediero A, Perez-Aso M, Cronstein BN (2013) Activation of adenosine A(2A) receptor reduces osteoclast formation via PKA- and ERK1/2-mediated suppression of NFkappaB nuclear translocation. Br J Pharmacol 169:1372–1388. https://doi.org/10.1111/bph.12227 CrossRefPubMedPubMedCentral

38.

Matyash M, Zabiegalov O, Wendt S, Matyash V, Kettenmann H (2017) The adenosine generating enzymes CD39/CD73 control microglial processes ramification in the mouse brain. PLoS One 12:e0175012. https://doi.org/10.1371/journal.pone.0175012 CrossRefPubMedPubMedCentral

39.

Loza MJ, Anderson AS, O'Rourke KS, Wood J, Khan IU (2011) T-cell specific defect in expression of the NTPDase CD39 as a biomarker for lupus. Cell Immunol 271:110–117. https://doi.org/10.1016/j.cellimm.2011.06.010 CrossRefPubMedPubMedCentral

40.

Herrath J, Chemin K, Albrecht I, Catrina AI, Malmstrom V (2014) Surface expression of CD39 identifies an enriched Treg-cell subset in the rheumatic joint, which does not suppress IL-17A secretion. Eur J Immunol 44:2979–2989. https://doi.org/10.1002/eji.201344140 CrossRefPubMed

41.

Guo H, Zheng M, Zhang K, Yang F, Zhang X, Han Q, Chen ZN, Zhu P (2016) Functional defects in CD4+ CD25high FoxP3+ regulatory cells in ankylosing spondylitis. Sci Rep 6:37559. https://doi.org/10.1038/srep37559 CrossRefPubMedPubMedCentral

42.

Moncrieffe H, Nistala K, Kamhieh Y, Evans J, Eddaoudi A, Eaton S, Wedderburn LR (2010) High expression of the ectonucleotidase CD39 on T cells from the inflamed site identifies two distinct populations, one regulatory and one memory T cell population. J Immunol 185:134–143. https://doi.org/10.4049/jimmunol.0803474 CrossRefPubMedPubMedCentral

Titel: Ankylosing spondylitis monocyte-derived macrophages express increased level of A2A adenosine receptor and decreased level of ectonucleoside triphosphate diphosphohydrolase-1 (CD39), A1 and A2B adenosine receptors
verfasst von: Maryam Akhtari
Seyed Jalal Zargar
Mahdi Mahmoudi
Mahdi Vojdanian
Alireza Rezaeimanesh
Ahmadreza Jamshidi
Publikationsdatum: 09.03.2018
Verlag: Springer London
Erschienen in: Clinical Rheumatology / Ausgabe 6/2018
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-018-4055-9

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

19.04.2024 | Vorhofflimmern | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Ankylosing spondylitis monocyte-derived macrophages express increased level of A_2A adenosine receptor and decreased level of ectonucleoside triphosphate diphosphohydrolase-1 (CD39), A₁ and A_2B adenosine receptors

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 6/2018

High burden of adverse events is associated with reduced remission rates in early rheumatoid arthritis

Ultrasound elastography-based assessment of the elasticity of the supraspinatus muscle in impingement syndrome: does elastography has any diagnostic value?

Age determines response to anti-TNFα treatment in patients with ankylosing spondylitis and is related to TNFα-producing CD8 cells

Long-term follow-up of paediatric MEFV carriers

Motion deficit in nodal interphalangeal joint osteoarthritis by digital goniometer in housewives

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Parodontalbehandlung verbessert Prognose bei Katheterablation

Antihypertensiva schützen auch alte Menschen noch vor Demenz

Stereotaktische Radiatio schlägt konventionelle Bestrahlung

Denken Sie bei starker Blutung auch an die Hemmkörper-Hämophilie

Update Innere Medizin