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

被引:97
作者
Secchiero, P
Corallini, F
di Iasio, MG
Gonelli, A
Barbarotto, E
Zauli, G
机构
[1] Univ Ferrara, Dept Morphol & Embryol, Human Anat Sect, I-44100 Ferrara, Italy
[2] Univ Trieste, Dept Normal Human Morphol, Trieste, Italy
关键词
D O I
10.1182/blood-2004-10-4111
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-alpha (40-fold) or interleukin 10 (IL-10; 20-fold). However, pretreatment of endothelial cultures with TRAIL determined a significant reduction of the proadhesive activity induced by both TNF-alpha and IL-1 beta. Unexpectedly, the antiadhesive activity of TRAIL was not due to interference with the nuclear factor kappa B (NF-kappa B)-mediated upregulation 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-alpha-induced chemokines, and, in particular, it abrogated the TNF-alpha-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-a. 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. (c) 2005 by The American Society of Hematology.
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页码:3413 / 3419
页数:7
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