Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces chemotactic migration of monocytes via a death receptor 4-mediated RhoGTPase pathway

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces
chemotactic migration of monocytes via a death receptor 4-mediated RhoGTPase pathway.

韋薇，王東生，史娟，項(xiàng)洋，張亞璽，劉士廉，劉彥信，鄭德先

Abstract
This study tested the hypothesis that TRAIL could play a role in regulating monocyte migration. TRAIL has been widely
studied for its anti-tumor function and signaling mechanisms. Using chemotaxis and mouse air-pouch model analyses, we
determined that TRAIL-induced chemotactic migration of THP-1 human leukemia and LPS-primed primary human monocytes as
well as LPS-stimulated BALB/c mouse monocytes in vivo. To expand the understanding of the TRAIL signaling pathway in this process, we found that the TRAIL receptor DR4 was highly expressed in THP-1 and LPS-primed primary monocytes but not in
the non-primed primary monocytes. DR4 neutralization antibody specifically suppressed TRAIL-induced migration of the
monocytes. Furthermore, PI3K, Rho GTPase and its downstream effectors, MLC and Pak1,were activated during cell migration.
PI3K inhibitors and dominant negative mutants of RhoGTPase blocked monocyte migration toward TRAIL, indicating that PI3K and RhoGTPases were involved in the migration signaling. The DR4 neutralization antibody blocked the activation of PI3K
and Rho GTPase effectors in the cells. Thus, these data support the hypothesis that TRAIL induces monocyte migration
mediated by TRAIL receptor DR4 via the RhoGTPase signaling pathway. This study is expected to provide novel evidence of
the non-apoptotic function of TRAIL in immune defense. Copyright © 2010 Elsevier Ltd. All rights reserved.