Unlike for Human Monocytes after LPS Activation, Release of TNF-[alpha] by THP-1 Cells Is Produced by a TACE Catalytically Different from Constitutive TACE

Tumor necrosis factor-alpha (TNF-[alpha]) is a pro-inflammatory cytokine today identified as a key mediator of several chronic inflammatory diseases. TNF-[alpha], initially synthesized as a membrane-anchored precursor (pro-TNF-[alpha]), is processed by proteolytic cleavage to generate the secreted m...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2012-03, Vol.7 (3), p.e34184
Main Authors: Moreira-Tabaka, Helena, Peluso, Jean, Vonesch, Jean-Luc, Hentsch, Didier, Kessler, Pascal, Reimund, Jean-Marie, Dumont, Serge, Muller, Christian D
Format: Article
Language:English
Subjects:
Proteases
Tumor necrosis factor
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tumor necrosis factor-alpha (TNF-[alpha]) is a pro-inflammatory cytokine today identified as a key mediator of several chronic inflammatory diseases. TNF-[alpha], initially synthesized as a membrane-anchored precursor (pro-TNF-[alpha]), is processed by proteolytic cleavage to generate the secreted mature form. TNF-[alpha] converting enzyme (TACE) is currently the first and single protease described as responsible for the inducible release of soluble TNF-[alpha]. Here, we demonstrated the presence on THP-1 cells as on human monocytes of a constitutive proteolytical activity able to cleave pro-TNF-[alpha]. 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-[alpha] 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-[alpha] release in LPS activated THP-1 cells, by contrast to human monocytes where the TACE activity remains catalytically unchanged even after LPS activation. On the surface of LPS activated THP-1 cells we identified a releasing TNF-[alpha] 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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0034184