Effects of biological drug adalimumab on tumour necrosis factor-alpha-converting enzyme activation

Immunology and Cell Biology
Sabrina Lisi, Margherita Sisto

Abstract

Tumour necrosis factor-alpha (TNF-alpha)-converting enzyme (TACE) is a membrane-bound metalloprotease and disintegrin. It is produced by a number of host cells and is known to shed and release cell-bound cytokines, particularly members of the TNF family. No investigations into the regulation of this enzyme by autoantibodies have been reported. In this study, we tested the hypothesis that anti-Ro/SSA autoantibodies, purified from IgG fractions of patients with primary Sjögren's syndrome, are capable to regulate TACE expression and activation in human salivary gland epithelial cells (SGEC). We also evaluated the potential physiological and therapeutic consequences of TNF-alpha blocking by the biological agent adalimumab, the first fully human (100% human peptide sequences) therapeutic anti-TNF-alpha antibody, on post-translational regulation of TACE. Taken together, our results show a dose-dependent increase in TACE expression in anti-Ro/SSA Abs-treated SGEC, followed by internalization, pro-domain shedding and activation of TACE protein. Adalimumab treatment brought TACE expression to levels than those observed in untreated SGEC. These findings, showing the presence of autoantibodies-dependent mechanisms by which TACE levels are...Continue Reading

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Citations

Feb 5, 2013·Journal of Molecular Histology·Margherita SistoMassimo D'Amore
Sep 3, 2010·Histochemistry and Cell Biology·Margherita SistoMassimo D'Amore
May 24, 2011·Histochemistry and Cell Biology·Margherita SistoMassimo D'Amore
Nov 12, 2014·International Reviews of Immunology·Margherita Sisto, Sabrina Lisi
Sep 22, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Margherita SistoMassimo D'Amore
Apr 18, 2012·International Journal of Immunopathology and Pharmacology·M CarlesimoA Arcese

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