Abstract
Toll-like receptor (TLR) activation and cytokines have been linked to the disease flare of systemic lupus erythematosus (SLE), yet the expression profiles of TLRs and cytokines in response to TLR activation in SLE patients remain unclear. In this study, we evaluated the expression levels of IL-10, TNF-α, interferon-γ (IFN-γ), TLR-2, TLR-4, and TLR-9 in peripheral blood mononuclear cells (PBMCs) from SLE patients and normal controls after PBMCs were stimulated with a TLR-2, TLR-4, or TLR-9 agonist. The expression levels in SLE patient group were statistically compared with those in normal control group. It was found in SLE patients that the IL-10 protein production was down-regulated after the activation of TLR-2, TLR-4, or TLR-9 and that the TNF-α protein production was decreased after the activation of TLR-2 or TLR-9, but not TLR-4. However, the transcript levels of IL-10 and TNF-α as well as the protein and transcript levels of IFN-γ were comparable between SLE and normal control groups. In addition, the TLR-2 transcript levels seem to be diminished after the activation of TLR-2, TLR-4, or TLR-9, but TLR-4 and TLR-9 transcript levels were not altered. The results indicate that the cytokine production from PBMCs in response to TLR activation is dysregulated in SLE patients, supporting the possibility that TLR activation may influence lupus disease activity through regulating cytokine production.
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References
Kumar H, Kawai T, Akira S (2009) Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388(4):621–625
Manicassamy S, Pulendran B (2009) Modulation of adaptive immunity with Toll-like receptors. Semin Immunol 21(4):185–193
McCormack W, Parker AE, O’Neill LA (2009) Toll-like receptors and NOD-like receptors in rheumatic diseases. Arthritis Res Ther 11(5):243
Iwasaki A, Medzhitov R (2010) Regulation of adaptive immunity by the innate immune system. Science 327(5963):291–295
Avalos AM, Busconi L, Marshak-Rothstein A (2010) Regulation of autoreactive B cell responses to endogenous TLR ligands. Autoimmunity 43(1):76–83
Lafyatis R, Marshak-Rothstein A (2007) Toll-like receptors and innate immune responses in systemic lupus erythematosus. Arthritis Res Ther 9(6):222
Bouza E, Moya JG, Muñoz P (2001) Infections in systemic lupus erythematosus and rheumatoid arthritis. Infect Dis Clin North Am 15(2):335–361
Juárez M, Misischia R, Alarcón GS (2003) Infections in systemic connective tissue diseases: systemic lupus erythematosus, scleroderma, and polymyositis/dermatomyositis. Rheum Dis Clin North Am 29(1):163–184
Yap DY, Lai KN (2010) Cytokines and their roles in the pathogenesis of systemic lupus erythematosus: from basics to recent advances. J Biomed Biotechnol 2010:365083
Llorente L, Richaud-Patin Y (2003) The role of interleukin-10 in systemic lupus erythematosus. J Autoimmun 20(4):287–289
Palucka AK, Blanck J-P, Bennett L, Pascual V, Banchereau J (2005) Cross-regulation of TNF and IFN-α in autoimmune diseases. Proc Natl Acad Sci USA 102(9):3372–3377
Morimoto S, Tokano Y, Nakano S, Watanabe T, Tamayama Y, Mitsuo A et al (2009) Chemoattractant mechanism of Th1 cells in class III and IV lupus nephritis. Autoimmunity 42(2):143–149
Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25(11):1271–1277
Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35(6):630–640
Roda JM, Parihar R, Carson WE 3rd (2005) CpG-containing oligodeoxynucleotides act through TLR9 to enhance the NK cell cytokine response to antibody-coated tumor cells. J Immunol 175(3):1619–1627
Ozato K, Tsujimura H, Tamura T (2002) Toll-like receptor signaling and regulation of cytokine gene expression in the immune system. Biotechniques Suppl:66–68, 70, 72 passim
Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376
Migita K, Miyashita T, Maeda Y, Nakamura M, Yatsuhashi H, Kimura H et al (2007) Toll-like receptor expression in lupus peripheral blood mononuclear cells. J Rheumatol 34(3):493–500
Komatsuda A, Wakui H, Iwamoto K, Ozawa M, Togashi M, Masai R et al (2008) Up-regulated expression of Toll-like receptors mRNAs in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Clin Exp Immunol 152(3):482–487
Marshak-Rothstein A (2006) Toll-like receptors in systemic autoimmune disease. Nat Rev Immunol 6(11):823–835
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This study has been supported by a grant from the joined research found of Cathay General Hospital and National Taiwan University.
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The authors declare that they have no conflict of interest related to the publication of this manuscript.
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Tsao, JT., Hsieh, SC., Chiang, BL. et al. Altered IL-10 and TNF-α production in peripheral blood mononuclear cells of systemic lupus erythematosus patients after Toll-like receptor 2, 4, or 9 activation. Clin Exp Med 12, 153–158 (2012). https://doi.org/10.1007/s10238-011-0161-6
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DOI: https://doi.org/10.1007/s10238-011-0161-6