%0 Journal Article
%T Unlike for Human Monocytes after LPS Activation, Release of TNF-¦Á by THP-1 Cells Is Produced by a TACE Catalytically Different from Constitutive TACE
%A Helena Moreira-Tabaka
%A Jean Peluso
%A Jean-Luc Vonesch
%A Didier Hentsch
%A Pascal Kessler
%A Jean-Marie Reimund
%A Serge Dumont
%A Christian D. Muller
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0034184
%X Background Tumor necrosis factor-alpha (TNF-¦Á) is a pro-inflammatory cytokine today identified as a key mediator of several chronic inflammatory diseases. TNF-¦Á, initially synthesized as a membrane-anchored precursor (pro-TNF-¦Á), is processed by proteolytic cleavage to generate the secreted mature form. TNF-¦Á converting enzyme (TACE) is currently the first and single protease described as responsible for the inducible release of soluble TNF-¦Á. Methodology/Principal Findings Here, we demonstrated the presence on THP-1 cells as on human monocytes of a constitutive proteolytical activity able to cleave pro-TNF-¦Á. Revelation of the cell surface TACE protein expression confirmed that the observed catalytic activity is due to TACE. However, further studies using effective and innovative TNF-¦Á inhibitors, as well as a highly selective TACE inhibitor, support the presence of a catalytically different sheddase activity on LPS activated THP-1 cells. It appears that this catalytically different TACE protease activity might have a significant contribution to TNF-¦Á release in LPS activated THP-1 cells, by contrast to human monocytes where the TACE activity remains catalytically unchanged even after LPS activation. Conclusions/Significance On the surface of LPS activated THP-1 cells we identified a releasing TNF-¦Á activity, catalytically different from the sheddase activity observed on human monocytes from healthy donors. This catalytically-modified TACE activity is different from the constitutive shedding activity and appears only upon stimulation by LPS.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0034184