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Research Article| Volume 44, ISSUE 6, P557-561, October 2012

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Altered IkBα expression promotes NF-kB activation in monocytes from primary Sjögren’s syndrome patients

  • Author Footnotes
    § these authors contributed equally and should be considered as first authors.
    Sabrina Lisi
    Correspondence
    Address for correspondence: Department of Basic Medical Sciences, Section of Human Anatomy, University of Bari, Piazza Giulio Cesare 1, I-70124 Bari, Italy
    Footnotes
    § these authors contributed equally and should be considered as first authors.
    Affiliations
    Department of Basic Medical Sciences, Section of Human Anatomy, Laboratory of Cell Biology, Italy
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  • Author Footnotes
    § these authors contributed equally and should be considered as first authors.
    Margherita Sisto
    Footnotes
    § these authors contributed equally and should be considered as first authors.
    Affiliations
    Department of Basic Medical Sciences, Section of Human Anatomy, Laboratory of Cell Biology, Italy
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  • Dario Domenico Lofrumento
    Affiliations
    Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy
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  • Massimo D’Amore
    Affiliations
    Department of Internal Medicine and Public Medicine, Section of Rheumatology, University of Bari Medical School, Bari, Italy
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  • Author Footnotes
    § these authors contributed equally and should be considered as first authors.
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      Summary

      Aims

      To study the importance of IkBα in NF-kB signal transduction, we analysed the IkBα expression in monocytes from Sjögren’s syndrome (SS) patients versus healthy controls.

      Methods

      Monocytes were obtained from the peripheral blood of 30 SS patients and 23 healthysubjects. I kBa expression was studied by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), real-time PCR, immunoblotting, flow cytometry and enzyme linked immunosorbent assay (ELISA).

      Results

      Analysis of the gene and protein expression profiles of SS monocytes revealed a down-regulation of IkBα, and in all the Sjögren’s syndrome cases examined, serum IkBa levels were significantly decreased in comparison with controls.

      Conclusions

      Our findings clearly demonstrate changes in the levels of IkBα in SS monocytes, suggesting that the attenuated expression of IkBα could contribute to the deregulation of NF-kB pathways in the SS pathogenesis. Decreased expression of IkBα may specifically amplify cytokines production and inflammatory response linked to Sjögren’s syndrome.

      Key words

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      References

        • Fox P.C.
        Autoimmune diseases and Sjögren’s syndrome: an autoimmune exocrinopathy.
        Ann N Y Acad Sci. 2007; 1098: 15-21
        • Azuma M.
        • Motegi K.
        • Aota K.
        • Hayashi Y.
        • Sato M.
        Role of cytokines in the destruction of acinar structure in Sjögren’s syndrome salivary glands.
        Lab Invest. 1997; 77: 269-280
        • Lisi S.
        • Sisto M.
        • Lofrumento D.D.
        • et al.
        Pro-inflammatory role of Anti-Ro/ SSA autoantibodies through the activation of Furin-TACE-amphiregulin axis.
        J Autoimmun. 2010; 35: 160-170
        • Barnes P.J.
        • Karin M.
        Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.
        N Engl J Med. 1997; 336: 1066-1071
        • Baeuerle P.A.
        Pro-inflammatory signaling: last pieces in the NFkappa B puzzle?.
        Curr Biol. 1998; 8: R19-R22
        • Tak P.P.
        • Firestein G.S.
        NF-kappa B: a key role in inflammatory diseases.
        J Clin Invest. 2001; 107: 7-11
        • Dale E.
        • Davis M.
        • Faustman D.L.
        A role for transcription factor NF-kappa B in autoimmunity: possible interactions of genes, sex, and the immune response.
        Adv Physiol Educ. 2006; 30: 152-158
        • Sisto M.
        • Lisi S.
        • Lofrumento D.D.
        • et al.
        A failure of TNFAIP3 negative regulation maintains sustained NF-KB activation in Sjögren’s syndrome.
        Histochem Cell Biol. 2011; 135: 615-625
        • Li Q.
        • Verma I.M.
        NF-kappa B regulation in the immune system.
        Nat Rev Immunol. 2002; 2: 725-734
        • Baldwin A.S.
        The NF-kB and IkB proteins: New discoveries and insights.
        Annu Rev Immunol. 1996; 14: 649-681
        • Foxwell B.
        • Browne K.
        • Bondeson J.
        • et al.
        Efficientadenoviralinfection with IkappaB alpha reveals that macrophage tumor necrosis factor alpha production in rheumatoid arthritis is NF-kappaB dependent.
        Proc Natl Acad Sci USA. 1998; 95: 8211-8215
        • Tas S.W.
        • Vervoordeldonk M.J.
        • Hajji N.
        • et al.
        Local treatment with the selective IkappaB kinase beta inhibitor NEMO-binding domain peptide ameliorates synovial inflammation.
        Arthritis Res Ther. 2006; 8: R86
        • Schneider C.
        • Strayhorn W.D.
        • Brantley D.M.
        • et al.
        Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice.
        J Invest Dermatol. 2004; 122: 691-698
        • Vitali C.
        • Bombardieri S.
        • Jonsson R.
        • et al.
        Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. European Study Group on Classification Criteria for Sjögren’s Syndrome.
        Ann Rheum Dis. 2002; 61: 554-558
        • Greenspan J.S.
        • Daniels T.E.
        • Talal N.
        • Sylvester R.A.
        The histopathology of Sjögren’s syndrome in labial salivary gland biopsies.
        Oral Surg Oral Med Oral Pathol. 1974; 37: 217-229
        • Sisto M.
        • Lisi S.
        • Castellana D.
        • et al.
        Autoantibodies from Sjögren’s syndrome induce activation of both the intrinsic and extrinsic apoptotic pathways in human salivary gland cell line A-253.
        J Autoimmun. 2006; 27: 38-49
        • Wildenberg M.E.
        • Welzen-Coppens J.M.
        • van Helden-Meeuwsen C.G.
        • et al.
        Increased frequency of CD16+ monocytes and the presence of activated dendritic cells in salivary glands in primary Sjögren syndrome.
        Ann Rheum Dis. 2009; 68: 420-426
        • Willeke P.
        • Gaubitz M.
        • Schotte H.
        • et al.
        Clinical and immunological characteristics of patients with Sjögren’s syndrome in relation to alpha- fodrin antibodies.
        Rheumatology (Oxford). 2007; 46: 479-483
        • Kimura-Shimmyo A.
        • Kashiwamura S.I.
        • Ueda H.
        • et al.
        Cytokine-induced injury of the lacrimal and salivary glands.
        J Immunother. 2002; 25: S42-S51
        • Yoshimoto K.
        • Tanaka M.
        • Kojima M.
        • et al.
        Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjögren’s syndrome.
        Arthritis Res Ther. 2011; 13: R170
        • Lawrence T.
        The nuclear factor NF-kappaB pathway in inflammation.
        Cold Spring Harb Perspect Biol. 2009; 1: a001651
        • Kumar A.
        • Takada Y.
        • Boriek A.M.
        • Aggarwal B.B.
        Nuclear factor-kappaB: its role in health and disease.
        J Mol Med. 2004; 82: 434-448
        • Jacobs M.D.
        • Harrison S.C.
        Structure of an IkappaBalpha/NF-kappaB complex.
        Cell. 1998; 95: 749-758
        • Beg A.A.
        • Finco T.S.
        • Nantermet P.V.
        • Baldwin A.S.
        Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of IkB: a mechanism for NF-KB activation.
        Mol Cell Biol. 1993; 13: 3301-3310
        • Lawrence T.
        • Fong C.
        The resolution of inflammation: anti-inflammatory roles for NF-kappaB.
        Int J Biochem Cell Biol. 2010; 42: 519-523
        • Yamamoto Y.
        • Gaynor R.B.
        Therapeutic potential of inhibition of the NF- kappaB pathway in the treatment of inflammation and cancer.
        J Clin Invest. 2001; 107: 135-142
        • Lisi S.
        • Sisto M.
        • Lofrumento D.D.
        • D’Amore M.
        Sjögren’s syndrome autoantibodies provoke changes in gene expression profiles of inflammatory cytokines triggering a pathway involving TACE/NF-KB.
        Lab Invest. 2012; 92: 615-624
        • Klement J.F.
        • Rice N.R.
        • Car B.D.
        • et al.
        IkappaBalpha deficiency results in a sustained NF-kappaB response and severe widespread dermatitis in mice.
        Mol Cell Biol. 1996; 16: 2341-2349