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Published in: Journal of Inflammation 1/2015

Open Access 01-12-2015 | Research

Reduced expression of peroxisome proliferator-activated receptor alpha in BAL and blood T cells of non-löfgren’s sarcoidosis patients

Authors: Muntasir Abo Al Hayja, Anders Eklund, Johan Grunewald, Jan Wahlström

Published in: Journal of Inflammation | Issue 1/2015

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Abstract

Background

Sarcoidosis is a granulomatous disease affecting in particular the lungs. The peroxisome proliferator-activated receptors (PPARs) play important regulatory roles in inflammation. The aim of this study was to gain more insight about the expression of all three PPARs (α, β/δ and γ) in sarcoidosis.

Methods

Bronchoalveolar lavage (BAL) cells and peripheral blood cells were obtained from healthy controls (HC) and sarcoidosis patients with Löfgren’s syndrome (LS) and without Löfgren’s syndrome (non-LS). PPARs mRNA expression was analyzed in total BAL cells and in FACS (Fluorescence-activated cell sorting) sorted alveolar macrophages (AM) and CD4+ T cells respectively by comparative RT-PCR. PPARs protein expression was analyzed in AM, and in BAL and blood CD4+ and CD8+ T cells by flow cytometry.

Results

In BAL CD4+ T cells, we noticed a significantly lower PPARα mRNA expression in sarcoidosis patients compared with HC. In non-LS patients, a significantly lower PPARα protein expression in BAL CD4+ T cells was detected as compared with LS patients. In peripheral blood CD4+ T cells, non-LS patients had a significantly lower expression of PPARα and PPARγ compared with LS patients.

Conclusion

The lower protein expression of PPARα and PPARγ could contribute to the persistent T-cell driven inflammation noted especially in non-resolving sarcoidosis, common in non-LS patients.
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Literature
1.
go back to reference Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Muller-Quernheim J. Lancet. 2014;383:1155–67. doi:10.1016/S0140-6736(13)60680-7.CrossRefPubMed Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet PY, Muller-Quernheim J. Lancet. 2014;383:1155–67. doi:10.1016/S0140-6736(13)60680-7.CrossRefPubMed
2.
go back to reference Touitou I. Inheritance of autoinflammatory diseases: shifting paradigms and nomenclature. J Med Genet. 2013;50(6):349–59. doi:10.1136/jmedgenet-2013-101577.CrossRefPubMed Touitou I. Inheritance of autoinflammatory diseases: shifting paradigms and nomenclature. J Med Genet. 2013;50(6):349–59. doi:10.1136/jmedgenet-2013-101577.CrossRefPubMed
3.
go back to reference Grunewald J. Review: role of genetics in susceptibility and outcome of sarcoidosis. Semin Respir Crit Care Med. 2010;31(04):380–9. doi:10.1055/s-0030-1262206.CrossRefPubMed Grunewald J. Review: role of genetics in susceptibility and outcome of sarcoidosis. Semin Respir Crit Care Med. 2010;31(04):380–9. doi:10.1055/s-0030-1262206.CrossRefPubMed
4.
go back to reference Bonifazi M, Bravi F, Gasparini S, La Vecchia C, Gabrielli A, Wells AU, et al. Sarcoidosis and cancer risk: systematic review and meta-analysis of observational studies. Chest. 2015;147(3):778–91. doi:10.1378/chest. 14–1475.CrossRefPubMed Bonifazi M, Bravi F, Gasparini S, La Vecchia C, Gabrielli A, Wells AU, et al. Sarcoidosis and cancer risk: systematic review and meta-analysis of observational studies. Chest. 2015;147(3):778–91. doi:10.1378/chest. 14–1475.CrossRefPubMed
5.
go back to reference Askling J, Grunewald J, Eklund A, Hillerdal G, Ekbom A. Increased risk for cancer following sarcoidosis. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1668–72. doi:10.1164/ajrccm.160.5.9904045.CrossRefPubMed Askling J, Grunewald J, Eklund A, Hillerdal G, Ekbom A. Increased risk for cancer following sarcoidosis. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1668–72. doi:10.1164/ajrccm.160.5.9904045.CrossRefPubMed
6.
go back to reference Belvisi MG, Hele DJ. Peroxisome proliferator-activated receptors as novel targets in lung disease. Chest. 2008;134(1):152–7. doi:10.1378/chest. 08–0019.CrossRefPubMed Belvisi MG, Hele DJ. Peroxisome proliferator-activated receptors as novel targets in lung disease. Chest. 2008;134(1):152–7. doi:10.1378/chest. 08–0019.CrossRefPubMed
7.
go back to reference Daynes RA, Jones DC. Emerging roles of ppars in inflammation and immunity. Nat Rev Immunol. 2002;2(10):748–59. doi:10.1038/nri912.CrossRefPubMed Daynes RA, Jones DC. Emerging roles of ppars in inflammation and immunity. Nat Rev Immunol. 2002;2(10):748–59. doi:10.1038/nri912.CrossRefPubMed
8.
go back to reference Grimaldi PA. Peroxisome proliferator-activated receptors as sensors of fatty acids and derivatives. Cell Mol Life Sci. 2007;64(19–20):2459–64. doi:10.1007/s00018-007-7278-5.CrossRefPubMed Grimaldi PA. Peroxisome proliferator-activated receptors as sensors of fatty acids and derivatives. Cell Mol Life Sci. 2007;64(19–20):2459–64. doi:10.1007/s00018-007-7278-5.CrossRefPubMed
9.
go back to reference Poulsen L, Siersbaek M, Mandrup S. PPARs: fatty acid sensors controlling metabolism. Semin Cell Dev Biol. 2012;23(6):631–9. doi:10.1016/j.semcdb.2012.01.003.CrossRefPubMed Poulsen L, Siersbaek M, Mandrup S. PPARs: fatty acid sensors controlling metabolism. Semin Cell Dev Biol. 2012;23(6):631–9. doi:10.1016/j.semcdb.2012.01.003.CrossRefPubMed
10.
go back to reference Straus DS, Glass CK. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol. 2007;28(12):551–8. doi:10.1016/j.it.2007.09.003.CrossRefPubMed Straus DS, Glass CK. Anti-inflammatory actions of PPAR ligands: new insights on cellular and molecular mechanisms. Trends Immunol. 2007;28(12):551–8. doi:10.1016/j.it.2007.09.003.CrossRefPubMed
11.
go back to reference al Yacoub N, Romanowska M, Krauss S, Schweiger S, Foerster J. PPARdelta is a type 1 IFN target gene and inhibits apoptosis in T cells. J Invest Dermatol. 2008;128(8):1940–9. doi:10.1038/jid.2008.32.CrossRefPubMed al Yacoub N, Romanowska M, Krauss S, Schweiger S, Foerster J. PPARdelta is a type 1 IFN target gene and inhibits apoptosis in T cells. J Invest Dermatol. 2008;128(8):1940–9. doi:10.1038/jid.2008.32.CrossRefPubMed
12.
go back to reference Culver DA, Barna BP, Raychaudhuri B, Bonfield TL, Abraham S, Malur A, et al. Peroxisome proliferator-activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis. Am J Respir Cell Mol Biol. 2004;30(1):1–5. doi:10.1165/rcmb.2003-0304RC.CrossRefPubMed Culver DA, Barna BP, Raychaudhuri B, Bonfield TL, Abraham S, Malur A, et al. Peroxisome proliferator-activated receptor gamma activity is deficient in alveolar macrophages in pulmonary sarcoidosis. Am J Respir Cell Mol Biol. 2004;30(1):1–5. doi:10.1165/rcmb.2003-0304RC.CrossRefPubMed
13.
go back to reference Barna BP, Culver DA, Abraham S, Malur A, Bonfield TL, John N, et al. Depressed peroxisome proliferator-activated receptor gamma (PPargamma) is indicative of severe pulmonary sarcoidosis: possible involvement of interferon gamma (IFN-gamma). Sarcoidosis Vasc Diffuse Lung Dis. 2006;23(2):93–100.PubMed Barna BP, Culver DA, Abraham S, Malur A, Bonfield TL, John N, et al. Depressed peroxisome proliferator-activated receptor gamma (PPargamma) is indicative of severe pulmonary sarcoidosis: possible involvement of interferon gamma (IFN-gamma). Sarcoidosis Vasc Diffuse Lung Dis. 2006;23(2):93–100.PubMed
14.
go back to reference Statement on sarcoidosis. Joint statement of the American thoracic society (ATS), the European respiratory society (ERS) and the world association of sarcoidosis and other granulomatous disorders (WASOG) adopted by the ATS board of directors and by the ERS executive committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736–55. doi:10.1164/ajrccm.160.2.ats4-99. Statement on sarcoidosis. Joint statement of the American thoracic society (ATS), the European respiratory society (ERS) and the world association of sarcoidosis and other granulomatous disorders (WASOG) adopted by the ATS board of directors and by the ERS executive committee, February 1999. Am J Respir Crit Care Med. 1999;160(2):736–55. doi:10.1164/ajrccm.160.2.ats4-99.
15.
go back to reference Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573–81. doi:10.1164/rccm.201006-0865CI.CrossRefPubMedCentralPubMed Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573–81. doi:10.1164/rccm.201006-0865CI.CrossRefPubMedCentralPubMed
16.
go back to reference Costabel U, Bonella F, Ohshimo S, Guzman J. Diagnostic modalities in sarcoidosis: BAL, EBUS, and PET. Semin Respir Crit Care Med. 2010;31(04):404–8. doi:10.1055/s-0030-1262207.CrossRefPubMed Costabel U, Bonella F, Ohshimo S, Guzman J. Diagnostic modalities in sarcoidosis: BAL, EBUS, and PET. Semin Respir Crit Care Med. 2010;31(04):404–8. doi:10.1055/s-0030-1262207.CrossRefPubMed
17.
go back to reference Eklund A, Blaschke E. Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis. Thorax. 1986;41(8):629–34.CrossRefPubMedCentralPubMed Eklund A, Blaschke E. Relationship between changed alveolar-capillary permeability and angiotensin converting enzyme activity in serum in sarcoidosis. Thorax. 1986;41(8):629–34.CrossRefPubMedCentralPubMed
18.
go back to reference Grunewald J, Berlin M, Olerup O, Eklund A. Lung T-helper cells expressing T-cell receptor AV2S3 associate with clinical features of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2000;161(3 Pt 1):814–8. doi:10.1164/ajrccm.161.3.9906001.CrossRefPubMed Grunewald J, Berlin M, Olerup O, Eklund A. Lung T-helper cells expressing T-cell receptor AV2S3 associate with clinical features of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2000;161(3 Pt 1):814–8. doi:10.1164/ajrccm.161.3.9906001.CrossRefPubMed
19.
go back to reference Kotecha N, Krutzik PO, Irish JM. Web-based analysis and publication of flow cytometry experiments. In: Paul Robinson J, editor. Current protocols in cytometry/editorial board. 2010. p. Chapter 10–Unit10 7. doi:10.1002/0471142956.cy1017s53. Kotecha N, Krutzik PO, Irish JM. Web-based analysis and publication of flow cytometry experiments. In: Paul Robinson J, editor. Current protocols in cytometry/editorial board. 2010. p. Chapter 10–Unit10 7. doi:10.1002/0471142956.cy1017s53.
20.
go back to reference Kriegova E, Arakelyan A, Fillerova R, Zatloukal J, Mrazek F, Navratilova Z, et al. PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells. BMC Mol Biol. 2008;9:69. doi:10.1186/1471-2199-9-69.CrossRefPubMedCentralPubMed Kriegova E, Arakelyan A, Fillerova R, Zatloukal J, Mrazek F, Navratilova Z, et al. PSMB2 and RPL32 are suitable denominators to normalize gene expression profiles in bronchoalveolar cells. BMC Mol Biol. 2008;9:69. doi:10.1186/1471-2199-9-69.CrossRefPubMedCentralPubMed
21.
go back to reference Livak K. Analysis of relative gene expression data using real-time quantitative PCR and the 2 − ΔΔCT method. Methods. 2001;25(4):402–8. doi:10.1006/meth.2001.1262.CrossRefPubMed Livak K. Analysis of relative gene expression data using real-time quantitative PCR and the 2 − ΔΔCT method. Methods. 2001;25(4):402–8. doi:10.1006/meth.2001.1262.CrossRefPubMed
22.
go back to reference Becker J, Delayre-Orthez C, Frossard N, Pons F. Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases? Fundam Clin Pharmacol. 2006;20(5):429–47. doi:10.1111/j.1472-8206.2006.00425.x.CrossRefPubMed Becker J, Delayre-Orthez C, Frossard N, Pons F. Regulation of inflammation by PPARs: a future approach to treat lung inflammatory diseases? Fundam Clin Pharmacol. 2006;20(5):429–47. doi:10.1111/j.1472-8206.2006.00425.x.CrossRefPubMed
24.
go back to reference Delayreorthez C, Becker J, Auwerx J, Frossard N, Pons F. Suppression of allergen-induced airway inflammation and immune response by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate. Eur J Pharmacol. 2008;581(1–2):177–84. doi:10.1016/j.ejphar.2007.11.040.CrossRef Delayreorthez C, Becker J, Auwerx J, Frossard N, Pons F. Suppression of allergen-induced airway inflammation and immune response by the peroxisome proliferator-activated receptor-alpha agonist fenofibrate. Eur J Pharmacol. 2008;581(1–2):177–84. doi:10.1016/j.ejphar.2007.11.040.CrossRef
25.
go back to reference Klotz L, Schmidt M, Giese T, Sastre M, Knolle P, Klockgether T, et al. Proinflammatory stimulation and pioglitazone treatment regulate peroxisome proliferator-activated receptor gamma levels in peripheral blood mononuclear cells from healthy controls and multiple sclerosis patients. J Immunol. 2005;175(8):4948–55.CrossRefPubMed Klotz L, Schmidt M, Giese T, Sastre M, Knolle P, Klockgether T, et al. Proinflammatory stimulation and pioglitazone treatment regulate peroxisome proliferator-activated receptor gamma levels in peripheral blood mononuclear cells from healthy controls and multiple sclerosis patients. J Immunol. 2005;175(8):4948–55.CrossRefPubMed
26.
go back to reference Dubuquoy L, Jansson EA, Deeb S, Rakotobe S, Karoui M, Colombel JF, et al. Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis. Gastroenterology. 2003;124(5):1265–76.CrossRefPubMed Dubuquoy L, Jansson EA, Deeb S, Rakotobe S, Karoui M, Colombel JF, et al. Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis. Gastroenterology. 2003;124(5):1265–76.CrossRefPubMed
27.
go back to reference Lakshmi SP, Reddy AT, Zhang Y, Sciurba FC, Mallampalli RK, Duncan SR, et al. Down-regulated peroxisome proliferator-activated receptor gamma (PPARgamma) in lung epithelial cells promotes a PPARgamma agonist-reversible proinflammatory phenotype in chronic obstructive pulmonary disease (COPD). J Biol Chem. 2014;289(10):6383–93. doi:10.1074/jbc.M113.536805.CrossRefPubMedCentralPubMed Lakshmi SP, Reddy AT, Zhang Y, Sciurba FC, Mallampalli RK, Duncan SR, et al. Down-regulated peroxisome proliferator-activated receptor gamma (PPARgamma) in lung epithelial cells promotes a PPARgamma agonist-reversible proinflammatory phenotype in chronic obstructive pulmonary disease (COPD). J Biol Chem. 2014;289(10):6383–93. doi:10.1074/jbc.M113.536805.CrossRefPubMedCentralPubMed
28.
go back to reference Idali F, Wiken M, Wahlstrom J, Mellstedt H, Eklund A, Rabbani H, et al. Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis. Eur Respir J. 2006;27(3):451–9. doi:10.1183/09031936.06.00067105.CrossRefPubMed Idali F, Wiken M, Wahlstrom J, Mellstedt H, Eklund A, Rabbani H, et al. Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis. Eur Respir J. 2006;27(3):451–9. doi:10.1183/09031936.06.00067105.CrossRefPubMed
29.
go back to reference Dubrac S, Elentner A, Schoonjans K, Auwerx J, Schmuth M. Lack of IL-2 in PPAR-alpha-deficient mice triggers allergic contact dermatitis by affecting regulatory T cells. Eur J Immunol. 2011;41(7):1980–91. doi:10.1002/eji.201041357.CrossRefPubMed Dubrac S, Elentner A, Schoonjans K, Auwerx J, Schmuth M. Lack of IL-2 in PPAR-alpha-deficient mice triggers allergic contact dermatitis by affecting regulatory T cells. Eur J Immunol. 2011;41(7):1980–91. doi:10.1002/eji.201041357.CrossRefPubMed
30.
go back to reference Guri AJ, Mohapatra SK. Horne 2nd WT, Hontecillas R. Bassaganya-Riera J The role of T cell PPAR gamma in mice with experimental inflammatory bowel disease BMC Gastroenterol. 2010;10:60. doi:10.1186/1471-230X-10-60. Guri AJ, Mohapatra SK. Horne 2nd WT, Hontecillas R. Bassaganya-Riera J The role of T cell PPAR gamma in mice with experimental inflammatory bowel disease BMC Gastroenterol. 2010;10:60. doi:10.1186/1471-230X-10-60.
31.
go back to reference Idali F, Wahlström J, Müller-Suur C, Eklund A, Grunewald J. Analysis of regulatory T cell associated forkhead box P3 expression in the lungs of patients with sarcoidosis. Clin Exp Immunol. 2008;152(1):127–37. doi:10.1111/j.1365-2249.2008.03609.x.CrossRefPubMedCentralPubMed Idali F, Wahlström J, Müller-Suur C, Eklund A, Grunewald J. Analysis of regulatory T cell associated forkhead box P3 expression in the lungs of patients with sarcoidosis. Clin Exp Immunol. 2008;152(1):127–37. doi:10.1111/j.1365-2249.2008.03609.x.CrossRefPubMedCentralPubMed
32.
go back to reference Tondell A, Moen T, Borset M, Salvesen O, Ro AD, Sue-Chu M. Bronchoalveolar lavage fluid IFN-gamma + Th17 cells and regulatory T cells in pulmonary sarcoidosis. Mediators Inflamm. 2014;2014:438070. doi:10.1155/2014/438070.CrossRefPubMedCentralPubMed Tondell A, Moen T, Borset M, Salvesen O, Ro AD, Sue-Chu M. Bronchoalveolar lavage fluid IFN-gamma + Th17 cells and regulatory T cells in pulmonary sarcoidosis. Mediators Inflamm. 2014;2014:438070. doi:10.1155/2014/438070.CrossRefPubMedCentralPubMed
33.
go back to reference Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, et al. The immune paradox of sarcoidosis and regulatory T cells. J Exp Med. 2006;203(2):359–70. doi:10.1084/jem.20050648.CrossRefPubMedCentralPubMed Miyara M, Amoura Z, Parizot C, Badoual C, Dorgham K, Trad S, et al. The immune paradox of sarcoidosis and regulatory T cells. J Exp Med. 2006;203(2):359–70. doi:10.1084/jem.20050648.CrossRefPubMedCentralPubMed
34.
go back to reference Huang H, Lu Z, Jiang C, Liu J, Wang Y, Xu Z. Imbalance between Th17 and regulatory T-Cells in sarcoidosis. Int J Mol Sci. 2013;14(11):21463–73. doi:10.3390/ijms141121463.CrossRefPubMedCentralPubMed Huang H, Lu Z, Jiang C, Liu J, Wang Y, Xu Z. Imbalance between Th17 and regulatory T-Cells in sarcoidosis. Int J Mol Sci. 2013;14(11):21463–73. doi:10.3390/ijms141121463.CrossRefPubMedCentralPubMed
35.
go back to reference Facco M, Cabrelle A, Teramo A, Olivieri V, Gnoato M, Teolato S, et al. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax. 2011;66(2):144–50. doi:10.1136/thx.2010.140319.CrossRefPubMed Facco M, Cabrelle A, Teramo A, Olivieri V, Gnoato M, Teolato S, et al. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax. 2011;66(2):144–50. doi:10.1136/thx.2010.140319.CrossRefPubMed
36.
go back to reference Ostadkarampour M, Eklund A, Moller D, Glader P, Olgart Hoglund C, Linden A, et al. Higher levels of interleukin IL-17 and antigen-specific IL-17 responses in pulmonary sarcoidosis patients with Lofgren’s syndrome. Clin Exp Immunol. 2014;178(2):342–52. doi:10.1111/cei.12403.CrossRefPubMed Ostadkarampour M, Eklund A, Moller D, Glader P, Olgart Hoglund C, Linden A, et al. Higher levels of interleukin IL-17 and antigen-specific IL-17 responses in pulmonary sarcoidosis patients with Lofgren’s syndrome. Clin Exp Immunol. 2014;178(2):342–52. doi:10.1111/cei.12403.CrossRefPubMed
37.
go back to reference Cosmi L, Santarlasci V, Maggi L, Liotta F, Annunziato F. Th17 plasticity: pathophysiology and treatment of chronic inflammatory disorders. Curr Opin Pharmacol. 2014;17C:12–6. doi:10.1016/j.coph.2014.06.004.CrossRef Cosmi L, Santarlasci V, Maggi L, Liotta F, Annunziato F. Th17 plasticity: pathophysiology and treatment of chronic inflammatory disorders. Curr Opin Pharmacol. 2014;17C:12–6. doi:10.1016/j.coph.2014.06.004.CrossRef
38.
go back to reference Lee JW, Bajwa PJ, Carson MJ, Jeske DR, Cong Y, Elson CO, et al. Fenofibrate represses interleukin-17 and interferon-gamma expression and improves colitis in interleukin-10-deficient mice. Gastroenterology. 2007;133(1):108–23. doi:10.1053/j.gastro.2007.03.113.CrossRefPubMed Lee JW, Bajwa PJ, Carson MJ, Jeske DR, Cong Y, Elson CO, et al. Fenofibrate represses interleukin-17 and interferon-gamma expression and improves colitis in interleukin-10-deficient mice. Gastroenterology. 2007;133(1):108–23. doi:10.1053/j.gastro.2007.03.113.CrossRefPubMed
39.
go back to reference da Rocha Junior LF, Rego MJ, Cavalcanti MB, Pereira MC, Pitta MG, de Oliveira PS, et al. Synthesis of a novel thiazolidinedione and evaluation of its modulatory effect on IFN- gamma, IL-6, IL-17A, and IL-22 production in PBMCs from rheumatoid arthritis patients. BioMed research international. 2013;2013:926060. doi:10.1155/2013/926060.CrossRefPubMedCentralPubMed da Rocha Junior LF, Rego MJ, Cavalcanti MB, Pereira MC, Pitta MG, de Oliveira PS, et al. Synthesis of a novel thiazolidinedione and evaluation of its modulatory effect on IFN- gamma, IL-6, IL-17A, and IL-22 production in PBMCs from rheumatoid arthritis patients. BioMed research international. 2013;2013:926060. doi:10.1155/2013/926060.CrossRefPubMedCentralPubMed
40.
go back to reference Klotz L, Burgdorf S, Dani I, Saijo K, Flossdorf J, Hucke S, et al. The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J Exp Med. 2009;206(10):2079–89. doi:10.1084/jem.20082771.CrossRefPubMedCentralPubMed Klotz L, Burgdorf S, Dani I, Saijo K, Flossdorf J, Hucke S, et al. The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J Exp Med. 2009;206(10):2079–89. doi:10.1084/jem.20082771.CrossRefPubMedCentralPubMed
41.
go back to reference de Sousa AR, Penalva LO, Marcotte EM, Vogel C. Global signatures of protein and mRNA expression levels. Mol Biosyst. 2009;5(12):1512–26. doi:10.1039/b908315d. de Sousa AR, Penalva LO, Marcotte EM, Vogel C. Global signatures of protein and mRNA expression levels. Mol Biosyst. 2009;5(12):1512–26. doi:10.1039/b908315d.
42.
go back to reference Albu DI, Califano D, Avram D. Flow cytometry analysis of transcription factors in T lymphocytes. Methods Mol Biol. 2010;647:377–90. doi:10.1007/978-1-60761-738-9_23.CrossRefPubMedCentralPubMed Albu DI, Califano D, Avram D. Flow cytometry analysis of transcription factors in T lymphocytes. Methods Mol Biol. 2010;647:377–90. doi:10.1007/978-1-60761-738-9_23.CrossRefPubMedCentralPubMed
43.
go back to reference Kanakasabai S, Chearwae W, Walline CC, Iams W, Adams SM, Bright JJ. Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis. Immunology. 2010;130(4):572–88. doi:10.1111/j.1365-2567.2010.03261.x.CrossRefPubMedCentralPubMed Kanakasabai S, Chearwae W, Walline CC, Iams W, Adams SM, Bright JJ. Peroxisome proliferator-activated receptor delta agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis. Immunology. 2010;130(4):572–88. doi:10.1111/j.1365-2567.2010.03261.x.CrossRefPubMedCentralPubMed
45.
go back to reference Malur A, McCoy AJ, Arce S, Barna BP, Kavuru MS, Malur AG, et al. Deletion of PPAR gamma in alveolar macrophages is associated with a Th-1 pulmonary inflammatory response. J Immunol. 2009;182(9):5816–22. doi:B10.4049/jimmunol.0803504.CrossRefPubMed Malur A, McCoy AJ, Arce S, Barna BP, Kavuru MS, Malur AG, et al. Deletion of PPAR gamma in alveolar macrophages is associated with a Th-1 pulmonary inflammatory response. J Immunol. 2009;182(9):5816–22. doi:B10.4049/jimmunol.0803504.CrossRefPubMed
46.
go back to reference Paramothayan NS, Lasserson TJ, Jones PW. Corticosteroids for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2005;2, CD001114. doi:10.1002/14651858.CD001114.pub2.PubMed Paramothayan NS, Lasserson TJ, Jones PW. Corticosteroids for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2005;2, CD001114. doi:10.1002/14651858.CD001114.pub2.PubMed
47.
go back to reference Paramothayan S, Lasserson TJ, Walters EH. Immunosuppressive and cytotoxic therapy for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2006;3, CD003536. doi:10.1002/14651858.CD003536.pub2.PubMed Paramothayan S, Lasserson TJ, Walters EH. Immunosuppressive and cytotoxic therapy for pulmonary sarcoidosis. Cochrane Database Syst Rev. 2006;3, CD003536. doi:10.1002/14651858.CD003536.pub2.PubMed
48.
go back to reference Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, et al. Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial. Gastroenterology. 2008;134(3):688–95. doi:10.1053/j.gastro.2007.12.012.CrossRefPubMedCentralPubMed Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, et al. Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled trial. Gastroenterology. 2008;134(3):688–95. doi:10.1053/j.gastro.2007.12.012.CrossRefPubMedCentralPubMed
49.
go back to reference Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharry C, et al. Bronchodilatory effect of the PPAR-γ agonist rosiglitazone in smokers with asthma. Clinical Pharmacology & Therapeutics. 2009;86(1):49–53. doi:10.1038/clpt.2009.41.CrossRef Spears M, Donnelly I, Jolly L, Brannigan M, Ito K, McSharry C, et al. Bronchodilatory effect of the PPAR-γ agonist rosiglitazone in smokers with asthma. Clinical Pharmacology & Therapeutics. 2009;86(1):49–53. doi:10.1038/clpt.2009.41.CrossRef
Metadata
Title
Reduced expression of peroxisome proliferator-activated receptor alpha in BAL and blood T cells of non-löfgren’s sarcoidosis patients
Authors
Muntasir Abo Al Hayja
Anders Eklund
Johan Grunewald
Jan Wahlström
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2015
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-015-0071-6

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