Interleukin 8 and cell migration to inflammatory sites: The regulation of focal adhesion kinase under conditions of migratory desensitization

Efrat Cohen-Hillel, Ilana Yron, Tsipi Meshel, Adit Ben-Baruch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Interleukin 8 is a prototypical inflammatory chemokine that induces leukocyte migration to inflammatory sites. Leukocyte recruitment in response to gradients of this chemokine is attenuated at advanced stages of inflammation to prevent damage to surrounding healthy tissues. Our published studies suggest that over-phosphorylation of focal adhesion kinase in migration-desensitizing conditions is involved in cessation of cell motility. This over-phosphorylation of FAK was induced by IL-8 only when the receptor transmitting the chemokine signals was CXCR2 and not CXCR1, indicating that the two IL-8 receptors diverge in their signaling properties. Objectives: To analyze the regulation of FAK in CXCR2-expressing hematopoeitic cells under conditions of migratory desensitization, focusing on the roles played by adhesion-related components in this process. Methods: Under conditions of migratory desensitization, we determined IL-8-induced cell spreading and FAK localization following disruption of actin filaments, and evaluated the role of integrins in FAK phosphorylation. Results: The disturbance of intact activity of actin filaments resulted in inhibition of cell spreading and modification of FAK intracellular localization upon IL-8 stimulation. Also, adhesion-dependent pre-stimulation of integrins was required for IL-8-induced FAK phosphorylation. Conclusions: Intact actin filaments and integrins are required for optimal IL-8-induced FAK phosphorylation in conditions of migratory desensitization. These observations suggest that lack of adequate activity/regulation of adhesion-related components may give rise to FAK activities that are not appropriately controlled, possibly leading to pathological conditions that are associated with perturbed leukocyte migration phenotypes.

Original languageEnglish
Pages (from-to)579-583
Number of pages5
JournalIsrael Medical Association Journal
Volume9
Issue number8
StatePublished - Aug 2007

Keywords

  • Actin filaments
  • Chemokines
  • Focal adhesion kinase
  • Integrins
  • Interleukin 8

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