TRAIL counteracts the proadhesive activity of inflammatory cytokines in endothelial cells by down-modulating CCL8 and CXCL10 chemokine expression and release

P Secchiero, F Corallini, MG di Iasio, A Gonelli… - Blood, 2005 - ashpublications.org
P Secchiero, F Corallini, MG di Iasio, A Gonelli, E Barbarotto, G Zauli
Blood, 2005ashpublications.org
Exposure of endothelial cells to recombinant tumor necrosis factor (TNF)-related apoptosis-
inducing ligand (TRAIL) induced a modest (2-fold) increase of HL-60 cell adhesion as
compared to TNF-α (40-fold) or interleukin 1β (IL-1β; 20-fold). However, pretreatment of
endothelial cultures with TRAIL determined a significant reduction of the proadhesive activity
induced by both TNF-α and IL-1β. Unexpectedly, the antiadhesive activity of TRAIL was not
due to interference with the nuclear factor κB (NF-κB)-mediated up-regulation of surface …
Abstract
Exposure of endothelial cells to recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced a modest (2-fold) increase of HL-60 cell adhesion as compared to TNF-α (40-fold) or interleukin 1β (IL-1β; 20-fold). However, pretreatment of endothelial cultures with TRAIL determined a significant reduction of the proadhesive activity induced by both TNF-α and IL-1β. Unexpectedly, the antiadhesive activity of TRAIL was not due to interference with the nuclear factor κB (NF-κB)-mediated up-regulation of surface intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin adhesion molecules in response to inflammatory cytokines. In searching for the molecular mechanism underlying this biologic activity of TRAIL, a cDNA microarray analysis was performed. TRAIL pretreatment variably down-modulated the mRNA steady-state levels of several TNF-α-induced chemokines, and, in particular, it abrogated the TNF-α-mediated up-regulation of CCL8 and CXCL10. Of note, the addition of optimal concentrations of recombinant CCL8 plus CXCL10 to endothelial cultures completely restored the proadhesive activity of TNF-α. Moreover, experiments performed with agonistic anti-TRAIL receptor antibodies demonstrated that both TRAIL-R1 and TRAIL-R2 contributed, although at different levels, to TRAIL-induced chemokine modulation. Taken together, our data suggest that TRAIL might play an important role in modulating leukocyte/endothelial cell adhesion by selectively down-regulating CCL8 and CXCL10 chemokines.
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