2010, Number 5
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Rev Invest Clin 2010; 62 (5)
Cyclooxigenase-2 polymoprhisms and bronchoalveolar lavage cellularity of Sarcoidosis
López-Campos JL, Rodríguez-Rodríguez D, Rodríguez-Becerra E, Alfageme-Michavila I, Fernández-Guerra J, García-Hernández FJ, Casanova Á, Fernández CJ, Romero-Ortiz A, Arellano-Orden E, Montes-Worboys A
Language: Spanish
References: 31
Page: 440-446
PDF size: 68.13 Kb.
ABSTRACT
Objectives. Recent studies have found cyclooxygenase-2 (COX-2) and its polymorphisms to be associated with sarcoidosis, being it significantly decreased in alveolar macrophages, with no information on the relationship between these polymorphisms and the rest of cells in bronchoalveolar lavage (BAL). The present study aimed to investigate the potential association between COX-2 gene polymorphisms and the BAL cell profile including the CD4/CD8 ratio.
Material and methods. This observational cross-sectional study involved six hospitals in Spain. Patients diagnosed with sarcoidosis with a BAL performed were included. The following variables were recorded: age, gender, initial diagnostic methods, serum angiotensin-converting enzyme levels, pulmonary function tests, radiological stage, and the cellularity and CD4/CD8 ratio from BAL. Genotyping of four COX-2 polymorphisms (COX2.5909T›G, COX2.8473T›C, COX2.926G›C, and COX2.3050G›C) was undertaken on DNA extracted from peripheral blood lymphocytes using fluorescent hybridization probes. The relationship between the polymorphisms and the cellularity was done by means of a multiple linear regression, adjusting for gender.
Results. A total of 51 sarcoid patients (23 males, mean age: 45 ± 15 years) were studied. CD4/CD8 ratio was significantly higher among homozygote allele C carriers of the polymorphism COX2.8473T›C (CC 11.2 ± 5.5
vs. CT+TT 4.4 ± 3.5; p = 0.022; β = 7.43; 95 % CI 1.38 – 13.48). Although several differences were observed in other cell groups, they did not reach the statistical significance level.
Conclusions. In patients diagnosed with sarcoidosis, there seems to be a relationship between COX2.8473 polymorphism and CD4/CD8 ratio from BAL.
REFERENCES
Charbeneau RP, Peters-Golden M. Eicosanoids: mediators and therapeutic targets in fibrotic lung disease. Clin Sci (Lond) 2005; 108: 479-91.
Hempel SL, Monick MM, Hunninghake GW. Lipopolysaccharide induces prostaglandin H synthase-2 protein and mRNA in human alveolar macrophages and blood monocytes. J Clin Invest 1994; 93: 391-6.
Pang L, Pitt A, Petkova D, Knox AJ. The COX-1/COX-2 balance in asthma. Clin Exp Allergy 1998; 28: 1050-8.
Brilla CG, Zhou G, Rupp H, Maisch B, Weber KT. Role of angiotensin II and prostaglandin E2 in regulating cardiac fibroblast collagen turnover. Am J Cardiol 1995; 76: 8D-13D.
Wilborn J, Crofford LJ, Burdick MD, Kunkel SL, Strieter RM, Peters-Golden M. Cultured lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis have a diminished capacity to synthesize prostaglandin E2 and to express cyclooxygenase-2. J Clin Invest 1995; 95: 1861-8.
Lama V, Moore BB, Christensen P, Toews GB, Peters-Golden M. Prostaglandin E2 synthesis and suppression of fibroblast proliferation by alveolar epithelial cells is cyclooxygenase-2- dependent. Am J Respir Cell Mol Biol 2002; 27: 752-8.
Wolter NJ, Kunkel SL, Lynch JP III, Ward PA. Production of cyclooxygenase products by alveolar macrophages in pulmonary sarcoidosis. Chest 1983; 83: 79S-81S.
Petkova DK, Clelland CA, Ronan JE, Lewis S, Knox AJ. Reduced expression of cyclooxygenase (COX) in idiopathic pulmonary fibrosis and sarcoidosis. Histopathology 2003; 43: 381-6.
Hill MR, Papafili A, Booth H, Lawson P, Hubner M, Beynon H, et al. Functional Prostaglandin-Endoperoxide Synthase 2 Polymorphism Predicts Poor Outcome in sarcoidosis. Am J Respir Crit Care Med 2006; 174: 915-22.
Lopez-Campos JL, Rodriguez-Rodriguez D, Rodriguez-Becerra E, Alfageme Michavila I, Guerra JF, Hernandez FJ, et al. Cyclooxygenase-2 polymorphisms confer susceptibility to sarcoidosis but are not related to prognosis. Respir Med 2009; 103: 427-33.
Statement on sarcoidosis. Am J Respir Crit Care Med 1999; 160: 736-55.
Costabel U. Sensitivity and specificity of BAL findings in sarcoidosis. Sarcoidosis 1992; 9(Suppl. 1): 211-4.
Siltzbach LE, James DG, Neville E, Turiaf J, Battesti JP, Sharma OP, et al. Course and prognosis of sarcoidosis around the world. Am J Med 1974; 57: 847-52.
Kilinc G, Kolsuk EA. The role of bronchoalveolar lavage in diffuse parenchymal lung diseases. Curr Opin Pulm Med 2005; 11: 417-21.
Skarke C, Schuss P, Kirchhof A, Doehring A, Geisslinger G, Lötsch J. Pyrosequencing of polymorphisms in the COX-2 gene (PTGS2) with reported clinical relevance. Pharmacogenomics 2007; 8: 1643-60.
Campa D, Zienolddiny S, Maggini V, Skaug V, Haugen A, Canzian F. Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Carcinogenesis 2004; 25: 229-35.
Bernard PB, Witter CT. Homogenous amplification and variant detection by fluorescent hybridization probes. Clin Chem 2000; 46: 147-8.
Fireman E, Boikaner T, Priel IE. Combined CD4/CD8 ratio in induced sputum and pulmonary function testing for non-invasive identification of sarcoidosis. Transl Res 2006; 148: 87-95.
Mrazek F, Holla LI, Hutyrova B, Znojil V, Vasku A, Kolek V, et al. Association of tumour necrosis factor-alpha, lymphotoxin- alpha and HLA-DRB1 gene polymorphisms with Lofgren’s syndrome in Czech patients with sarcoidosis. Tissue Antigens 2005; 65: 163-71.
Spagnolo P, Sato H, Marshall SE, Antoniou KM, Ahmad T, Wells AU, et al. Association between heat shock protein 70/ Hom genetic polymorphisms and uveitis in patients with sarcoidosis. Invest Ophthalmol Vis Sci 2007; 48: 3019-25.
Hizawa N, Yamaguchi E, Furuya K, Jinushi E, Ito A, Kawakami Y. The role of the C-C chemokine receptor 2 gene polymorphism V64I (CCR2-64I) in sarcoidosis in a Japanese population. Am J Respir Crit Care Med 1999; 159: 2021-23.
Furuya K, Yamaguchi E, Kawakami Y. [Angiotensin-converting enzyme (ACE) polymorphism and serum ACE activities in sarcoidosis]. Nippon Rinsho 1994; 52: 1561-66.
Grunewald J, Wahlstrom J, Berlin M, Wigzell H, Eklund A, Olerup O. Lung restricted T cell receptor AV2S3+ CD4+ T cell expansions in sarcoidosis patients with a shared HLA-DRbeta chain conformation. Thorax 2002; 57: 348-52.
Roberts SD, Kohli LL, Wood KL, Wilkes DS, Knox KS. CD4+CD28-T cells are expanded in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2005; 22: 13-9.
Fernández-Villar A, Botana MI, Leiro V, Represas C, González A, Mosteiro M, Piñeiro L. Utilidad clinica de la puncion transbronquial de adenopatias mediastinicas en el diagnostico de la sarcoidosis en estadios I y II. Arch Bronconeumol 2007; 43: 495-500.
Nagai S, Izumi T. Bronchoalveolar lavage. Still useful in diagnosing sarcoidosis? Clin Chest Med 1997; 18: 787-97.
Bacha D, Ayadi-Kaddour A, Ismail O, El Mezni F. Bronchoalveolar lavage impact in sarcoidosis: study of 40 cases. Tunis Med 2009; 87: 38-42.
Schildge J, Nagel C, Grun C. Bronchoalveolar lavage in interstitial lung diseases: does the recovery rate affect the results? Respiration 2007; 74: 553-7.
Stenson WF, Parker CW. Prostaglandins, macrophages, and immunity. J Immunol 1980; 125: 1-5.
Lama V, Moore BB, Christensen P, Toews GB, Peters-Golden M. Prostaglandin E2 synthesis and suppression of fibroblast proliferation by alveolar epithelial cells is cyclooxygenase-2- dependent. Am J Respir Cell Mol Biol 2002; 27: 752-8.
López-Campos Bodineau JL, García Polo C, León Jiménez A. Fármacos inhibidores de la agregación plaquetaria y sangrado en broncoscopia. Neumosur 2006; 18: 94-101.