IFN-gamma and STAT1 arrest monocyte migration and modulate RAC/CDC42 pathways. Academic Article uri icon

Overview

abstract

  • Positive regulation of cell migration by chemotactic factors and downstream signaling pathways has been extensively investigated. In contrast, little is known about factors and mechanisms that induce migration arrest, a process important for retention of cells at inflammatory sites and homeostatic regulation of cell trafficking. In this study, we found that IFN-gamma directly inhibited monocyte migration by suppressing remodeling of the actin cytoskeleton and cell polarization in response to the chemokine CCL2. Inhibition was dependent on STAT1 and downstream genes, whereas STAT3 promoted migration. IFN-gamma altered monocyte responses to CCL2 by modulating the activity of Pyk2, JNK, and the GTPases Rac and Cdc42, and inhibiting CCL2-induced activation of the downstream p21-activated kinase that regulates the cytoskeleton and cell polarization. These results identify a new role for IFN-gamma in arresting monocyte chemotaxis by a mechanism that involves modulation of cytoskeleton remodeling. Crosstalk between Jak-STAT and Rac/Cdc42 GTPase-mediated signaling pathways provides a molecular mechanism by which cytokines can regulate cell migration.

publication date

  • June 15, 2008

Research

keywords

  • Cell Migration Inhibition
  • Interferon-gamma
  • Monocytes
  • STAT1 Transcription Factor
  • Signal Transduction
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins

Identity

PubMed Central ID

  • PMC2742170

Scopus Document Identifier

  • 50949121438

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.180.12.8057

PubMed ID

  • 18523269

Additional Document Info

volume

  • 180

issue

  • 12