The online version of this article (doi:10.1186/1476-9255-9-3) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
AH, KH: participated in the design and coordination of the study and to manuscript writing, performed the experiments and analyzed the data. AB, JA and HA: participated in the design, coordination of the study and analyzed the data. All authors read and approved the final manuscript.
Excessive Th1 cells and TLRs functions are involved in the pathogenesis of Behcet's disease (BD) in response to bacterial antigens. NOD2, an intracellular pathogen recognition sensor, modulates innate defence to muropeptides derived from various bacterial species. To further define a role for NOD2 in BD, we analysed NOD2 transcriptional responses in BAL-MNC from BD patients with pulmonary manifestations.
We analysed NOD1, NOD2, T-bet and TLRs mRNA expression with real-time polymerase chain-reaction in BAL cells obtained from 23 BD patients with pulmonary manifestations and their matched controls.
We found that NOD2 mRNA expression was highly up-regulated in BAL cells from BD and sarcoidosis patients compared to healthy control group (P = 0.001). In BD patients, significant correlation was found between NOD2 and T-bet mRNA expression (r = 0.602; P = 0.0009). In BAL from BD patients, NOD2 and T-bet mRNA expression were significantly correlated with BAL-lymphocytes (r = 0.485, P = 0.010; r = 0684, P = 0.0001 respectively). NOD2 in BD was also correlated with TLR 2(r = 0.444; P = 0.021) and TLR 4 (r = 0.574; P = 0.001) mRNA expression.
Our results indicate that BAL-MNC from BD patients expressed NOD2 as a result of lung inflammation. TLRs and NOD2 synergize for the induction of proinflammatory cytokines. BAL inflammatory cells showed an increased Th1 situation as indicated by increased T-bet mRNA expression.
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Mumcu G, Inanc N, Yavuz S, Direskeneli H: The role of infectious agents in the pathogenesis, clinical manifestations and treatment strategies in Behcet's disease. Clin Exp Rheumatol. 2007, 25: S27-S33. PubMed
Pervin K, Childrstone A, Shinnick T, Mizushima Y, Van der-Zee R, Hasan A, Vaughan R, Lehner T: T cell epitope expression of mycobacterial and homologous human 65-kilodalton heat shock protein peptides in short term cell lines from patients with Behcet's disease. J Immunol. 1993, 151: 2273-2282. PubMed
Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nunez G: Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn's disease. J Biol Chem. 2003, 278: 5509-5512. 10.1074/jbc.C200673200. CrossRefPubMed
Billmann-Born S, Till A, Arlt A, Lipinski S, Sina C, Latiano A, Annese V, Häsler R, Kerick M, Manke T, Seegert D, Hanidu A, Schäfer H, Van-Heel D, Li J, Schreiber S, Rosenstiel P: Genome-Wide Expression Profiling Identifies an Impairment of Negative Feedback Signals in the Crohn's Disease-Associated: NOD2 Variant L1007fsinsC. J Immunol. 2011, 186: 4027-4038. 10.4049/jimmunol.1000085. CrossRefPubMed
International study group for Behcet's disease: Criteria for diagnosis of Behcet's disease. Lancet. 1990, 335: 1078-1080.
Hamzaoui A, Ghraïri H, Ammar J, Zekri S, Guemira F, Hamzaoui K: IL-18 mRNA expression and IFN-gamma induction in bronchoalveolar lavage from Behçet's disease. Clin Exp Rheumatol. 2003, 21: S8-S14. PubMed
American Thoracic Society, European Respiratory Society and World Association of Sarcoidosis and Other Granulomatous Disorders: Joint Statement on sarcoidosis. Am J Respir Crit Care Med. 1999, 160: 736-755. CrossRef
Dheda K, Huggett JF, Bustin SA, Johnson MA, Rook G, Zumla A: Validation of housekeeping genes for normalizing RNA expression in real-time PCR. Biotechniques. 2004, 37: 112-114. 116, 118-9. PubMed
Direskeneli H, Saruhan-Direskeneli G: The role of heat shock proteins in Behçet's disease. Clin Exp Rheumatol. 2003, 21: S44-S48. PubMed
Ferrante A, Ciccia F, Principato A, Giardina AR, Impastato R, Peralta S, Triolo G: A Th1 but not a Th17 response is present in the gastrointestinal involvement of Behçet's disease. Clin Exp Rheumatol. 2010, 28: S27-S30. PubMed
Hamzaoui K, Bouali E, Ghorbel I, Khanfir M, Hamzaoui A: Expression of Th-17 and RORγt mRNA in Behçet's Disease. Med Sci Monit. 2011, 17: 227-234. CrossRef
Matsuoka K, Inoue N, Sato T, Okamoto S, Hisamatsu T, Kishi Y, Sakuraba A, Hitotsumatsu O, Ogata H, Koganei K, Fukushima T, Kanai T, Watanabe M, Ishii H, Hibi T: T-bet upregulation and subsequent interleukin 12 stimulation are essential for induction of Th1 mediated immunopathology in Crohn's disease. Gut. 2004, 53: 1303-1308. 10.1136/gut.2003.024190. PubMedCentralCrossRefPubMed
Turan B, Pfister K, Diener PA, Hell M, Möller B, Boyvat A, Ergin S, Villiger PM: Soluble tumour necrosis factor receptors sTNFR1 and sTNFR2 are produced at sites of inflammation and are markers of arthritis activity in Behçet's disease. Scand J Rheumatol. 2008, 37: 135-141. 10.1080/03009740701747137. CrossRefPubMed
Uyar FA, Saruhan-Direskeneli G, Gül A: Common Crohn's disease-predisposing variants of the CARD15/NOD2 gene are not associated with Behçet's disease in Turkey. Clin Exp Rheumatol. 2004, 22 (4 Suppl 34): 50-52.
Kappen JH, Wallace GR, Stolk L, Rivadeneira F, Uitterlinden AG, Van-Daele PL, Laman JD, Kuijpers RW, Baarsma GS, Stanford MR, Fortune F, Madanat W, Van-Hagen PM, Van-Laar JA: Low prevalence of NOD2 SNPs in Behçet's disease suggests protective association in Caucasians. Rheumatology (Oxford). 2009, 48 (11): 1375-1377. 10.1093/rheumatology/kep292. CrossRef
Lafferty EI, Qureshi ST, Schnare M: The role of toll-like receptors in acute and chronic lung inflammation. J Inflamm (Lond). 2010, 7: 57-69. 10.1186/1476-9255-7-57. CrossRef
Durrani O, Banahan K, Sheedy FJ, McBride L, Ben-Chetrit E, Greiner K, Vaughan RW, Kondeatis E, Hamburger J, Fortune F, Stanford MR, Murray PI, O'Neill LA, Wallace GR: TIRAP Ser180Leu polymorphism is associated with Behcet's disease. Rheumatology (Oxford). 2011, 50 (10): 1760-1765. 10.1093/rheumatology/ker200. CrossRef
Kirino Y, Takeno M, Watanabe R, Murakami S, Kobayashi M, Ideguchi H, Ihata A, Ohno S, Ueda A, Mizuki N, Ishigatsubo Y: Association of reduced heme oxygenase-1 with excessive Toll-like receptor 4 expression in peripheral blood mononuclearcells in Behçet's disease. Arthritis Res Ther. 2008, 10: R16-10.1186/ar2367. PubMedCentralCrossRefPubMed
- NOD2 is highly expressed in Behçet disease with pulmonary manifestations
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