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.
Fiche publication
Date publication
janvier 2012
Auteurs
Membres identifiés du Cancéropôle Est :
Dr MULLER Christian, Dr VONESCH Jean-Luc, Pr REIMUND Jean-Marie
Tous les auteurs :
Moreira-Tabaka H, Peluso J, Vonesch JL, Hentsch D, Kessler P, Reimund JM, Dumont S, Muller CD
Lien Pubmed
Résumé
BACKGROUND: 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. 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-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. CONCLUSIONS/SIGNIFICANCE: 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.
Référence
PLoS One. 2012;7(3):e34184