Abstracts
Toll-like receptors (TLRs) have been found to contribute to the pathogenesis of rheumatoid arthritis (RA). The aim of this study is to investigate the regulation and potential role of TLR2 in spleen of pristane-induced arthritis (PIA) rat, which can be used to further understand the mechanisms of RA. Arthritis in DA rats was induced by pristane. TLR2 expression in spleen was detected by real-time quantitative PCR and western blotting, and TLR2 expression at both mRNA and protein levels was upregulated in PIA rats. Peptidoglycan (PGN) was systemically administrated to PIA rats, and arthritis severity was evaluated macroscopically and microscopically. Results showed that systemic administration of PGN to PIA rats obviously deteriorated arthritis severity. TLR2 expression on splenocytes and different types of immune cells was measured by flow cytometry. And it was found that TLR2 was mainly expressed on antigen-presenting cells (APCs) of spleen, and the proportion of TLR2+ dendritic cells and macrophages in spleen of PIA rats was increased remarkably. Thus, we conclude that the induction of TLR2+ APCs in spleen may participate in the maintenance of PIA.
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References
Iwasaki A, Medzhitov R (2004) Toll-like receptor control of the adaptive immune responses. Nat Immunol 5(10):987–995. doi:10.1038/ni1112
Barton GM, Medzhitov R (2003) Toll-like receptor signaling pathways. Science 300(5625):1524–1525
Huang QQ, Sobkoviak R, Jockheck-Clark AR, Shi B, Mandelin AM, Tak PP, Haines GK, Nicchitta CV, Pope RM (2009) Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J Immunol 182(8):4965–4973. doi:10.4049/jimmunol.0801563
Noronha AM, Liang YM, Farraye FA, Becker JM, Stucchi A, Ganley-Leal LM (2009) TLR2 regulates B cell response and function in inflammatory bowel disease. Gastroenterology 136(5):A258–A268
Correale J, Farez M (2009) Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms. J Immunol 183(9):5999–6012. doi:10.4049/jimmunol.0900897
Bjornvold M, Munthe-Kaas MC, Egeland T, Joner G, Dahl-Jorgensen K, Njolstad PR, Akselsen HE, Gervin K, Carlsen KCL, Carlsen KH, Undlien DE (2009) A TLR2 polymorphism is associated with type 1 diabetes and allergic asthma. Genes Immun 10(2):181–187. doi:10.1038/gene.2008.100
Meng L, He X, Zhu W, Yang X, Jiang C, Sun Q, Asim RMB, Zhang S, Xue Q, Xie X, Lu S (2011) TLR3 and TLR7 modulate IgE production in antigen induced pulmonary inflammation via influencing IL-4 expression in immune organs. PLoS One. doi:10.1371/journal.pone.0017252
Lee DM, Weinblatt ME (2001) Rheumatoid arthritis. Lancet 358(9285):903–911
Radstake T, Roelofs MF, Jenniskens YA, Oppers-Walgreen B, van Riel P, Barrera P, Joosten LAB, van den Berg WB (2004) Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum 50(12):3856–3865. doi:10.1002/art.20678
Seibl R, Birchler T, Loeliger S, Hossle JP, Gay RE, Saurenmann T, Michel BA, Seger RA, Gay S, Lauener RP (2003) Expression and regulation of toll-like receptor 2 in rheumatoid arthritis synovium. Am J Pathol 162(4):1221–1227
van der Heijden IM, Wilbrink B, Tchetverikov I, Schrijver IA, Schouls LM, Hazenberg MP, Breedveld FC, Tak PP (2000) Presence of bacterial DNA and bacterial peptidoglycans in joints of patients with rheumatoid arthritis and other arthritides. Arthritis Rheum 43(3):593–598
Young Ok Jung M-LC, Kang C-M, Jhun J-Y, Park J-S, Oh H-J, Min J-K, Park S-H, Kim H-Y (2007) Toll-like receptor 2 and 4 combination engagement upregulate IL-15 synergistically in human rheumatoid synovial fibroblasts. Immunol Lett 109(1):21–27
Pierer M, Rethage J, Seibl R, Lauener R, Brentano F, Wagner U, Hantzschel H, Michel BA, Gay RE, Gay S, Kyburz D (2004) Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by toll-like receptor 2 ligands. J Immunol 172(2):1256–1265
Huang QQ, Ma YY, Adebayo A, Pope RM (2007) Increased macrophage activation mediated through toll-like receptors in rheumatoid arthritis. Arthritis Rheum 56(7):2192–2201. doi:10.1002/art.22707
Liu ZQ, Deng GM, Foster S, Tarkowski A (2001) Staphylococcal peptidoglycans induce arthritis. Arthritis Res 3(6):375–380
Arend WP (2001) The innate immune system in rheumatoid arthritis. Arthritis Rheum 44(10):2224–2234
Ji H, Ohmura K, Mahmood U, Lee DM, Hofhuis FM, Boackle SA, Takahashi K, Holers VM, Walport M, Gerard C, Ezekowitz A, Carroll MC, Brenner M, Weissleder R, Verbeek JS, Duchatelle V, Degott C, Benoist C, Mathis D (2002) Arthritis critically dependent on innate immune system players. Immunity 16(2):157–168
Meng LS, Zhu WH, Jiang CS, He XJ, Hou WK, Zheng F, Holmdahl R, Lu SM (2010) Toll-like receptor 3 upregulation in macrophages participates in the initiation and maintenance of pristane-induced arthritis in rats. Arthritis Res Ther. doi:10.1186/ar3034
Vingsbo C, Sahlstrand P, Brun JG, Jonsson R, Saxne T, Holmdahl R (1996) Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. Am J Pathol 149(5):1675–1683
Hoffmann MH, Tuncel J, Skriner K, Tohidast-Akrad M, Tuerk B, Pinol-Roma S, Serre G, Schett G, Smolen JS, Holmdahl R, Steiner G (2007) The rheumatoid arthritis-associated autoantigen hnRNP-A2 (RA33) is a major stimulator of autoimmunity in rats with pristane-induced arthritis. J Immunol 179(11):7568–7576
Hou W, Meng L, Tian L, Zhu W, Jiang C, Lu S (2010) A systematic comparison between collagen-induced arthritis and pristane-induced arthritis in Dark Agouti rats. Clin Exp Rheumatol 28(4):532–538
Holmberg J, Tuncel J, Yamada H, Lu SM, Olofsson P, Holmdahl R (2006) Pristane, a non-antigenic adjuvant, induces MHC class II-restricted, arthritogenic T cells in the rat. J Immunol 176(2):1172–1179
Iwahashi M, Yamamura M, Aita T, Okamoto A, Ueno A, Ogawa N, Akashi S, Miyake K, Godowski PJ, Makino F (2004) Expression of toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis. Arthritis Rheum 50(5):1457–1467. doi:10.1002/art.20219
Frasnelli ME, Tarussio D, Chobaz-Peclat V, Busso N, So A (2005) TLR2 modulates inflammation in zymosan-induced arthritis in mice. Arthritis Res Ther 7(2):R370–R379. doi:10.1186/ar1494
Abdollahi-Roodsaz S, Joosten LAB, Koenders MI, Devesa I, Roelofs MF, Radstake T, Heuvelmans-Jacobs M, Akira S, Nicklin MJH, Ribeiro-Dias F, Van den Berg WB (2008) Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis. J Clin Invest 118(1):205–216. doi:10.1172/jci32639
Puliti M, Uematsu S, Akira S, Bistoni F, Tissi L (2009) Toll-like receptor 2 deficiency is associated with enhanced severity of group B streptococcal disease. Infect Immun 77(4):1524–1531. doi:10.1128/iai.00965-08
Hopkins PA, Sriskandan S (2005) Mammalian toll-like receptors: to immunity and beyond. Clin Exp Immunol 140(3):395–407. doi:10.1111/j.1365-2249.2005.02801.x
Acknowledgments
We should express gratitude to Mr. Fujun Zhang, Ms.Yan Han and Qilan Ning for their expertise and assistance in the experiments. The work was supported by grants from the National Natural Science Foundation of China (30801027, 30630058 and 81070030).
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Zhu, W., Meng, L., Jiang, C. et al. Induction of toll-like receptor 2 positive antigen-presenting cells in spleen of pristane-induced arthritis in rats. Mol Biol Rep 39, 3667–3673 (2012). https://doi.org/10.1007/s11033-011-1141-3
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DOI: https://doi.org/10.1007/s11033-011-1141-3