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Sisto M, Lisi S, Lofrumento DD, et al. RETRACTED: Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies. Lab Invest. 2010;doi: 10.1038/labinvest.2010.168.
Sisto, M., Lisi, S., Lofrumento, D. D., Cucci, L., Mitolo, V., & D'Amore, M. (2010). RETRACTED: Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies. Laboratory investigation; a journal of technical methods and pathology, . https://doi.org/10.1038/labinvest.2010.168
Sisto, Margherita, et al. "RETRACTED: Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies." Laboratory investigation; a journal of technical methods and pathology vol. (2010). doi: https://doi.org/10.1038/labinvest.2010.168
Sisto M, Lisi S, Lofrumento DD, Cucci L, Mitolo V, D'Amore M. RETRACTED: Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies. Lab Invest. 2010 Sep 20; doi: 10.1038/labinvest.2010.168. Epub 2010 Sep 20. PMID: 20856228.
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Lab Invest. 2010 Sep 20; doi: 10.1038/labinvest.2010.168. Epub 2010 Sep 20.

RETRACTED: Blockade of TNF-α signaling suppresses the AREG-mediated IL-6 and IL-8 cytokines secretion induced by anti-Ro/SSA autoantibodies.

Laboratory investigation; a journal of technical methods and pathology

Margherita Sisto, Sabrina Lisi, Dario Domenico Lofrumento, Liana Cucci, Vincenzo Mitolo, Massimo D'Amore

Affiliations

  1. Laboratory of Cell Biology, Department of Human Anatomy and Histology, University of Bari Medical School, Bari, Italy.

PMID: 20856228 DOI: 10.1038/labinvest.2010.168

Abstract

The aim of this study was to analyze the Furin-TNF-α-converting enzyme (TACE)-amphiregulin (AREG)-IL-6/IL-8 secretion pathway in non-neoplastic human salivary gland epithelial cells (SGECs) stimulated with anti-Ro/SSA autoantibodies (Abs). We examined whether anti-Ro/SSA Abs-mediated TACE activation is responsible for AREG activation. As recent studies have demonstrated that AREG could induce proinflammatory cytokines secretion in epithelial cells, we discuss how TACE-mediated AREG shedding, caused by anti-Ro/SSA Abs treatment, could have a critical role in TNF-α-induced IL-6 and IL-8 secretion by SGEC. Furthermore, the effects of TNF-α blockade on AREG expression and TNF-α-AREG-mediated IL-6 and IL-8 secretion were evaluated. We have discovered that the upregulation of AREG occurs through TNF-α produced after anti-Ro/SSA Abs uptake via Fcγ receptors. Biological drug adalimumab and the gene silencing technique were used to study the AREG-IL-6/IL-8 secretion pathway, demonstrating that (i) adalimumab-mediated TNF-α blocking and TNF-α gene silencing provoke a significant decrease of proinflammatory cytokines production and AREG expression in anti-Ro/SSA Abs-treated SGEC; (ii) AREG gene silencing has a potent inhibitory effect on TNF-α-induced IL-6 and IL-8 secretion in SGEC treated with anti-Ro/SSA Abs; (iii) an inspection of the kinetics of cytokine production after exogeni TNF-α and AREG addition, and the use of cycloheximide in the presence of exogenous TNF-α as stimulant, clarified that TNF-α induces IL-6 and IL-8 secretion through AREG.Laboratory Investigation advance online publication, 20 September 2010; doi:10.1038/labinvest.2010.168.

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