title: Interleukin 8 and cell migration to inflammatory sites: the regulation of focal adhesion kinase under conditions of migratory desensitization.
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.
  
  
  OBJECTIVE
  To analyze the regulation of FAK in CXCR2-expressing hematopoietic 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.
authors: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Israel.
authors: Efrat
authors: E
authors: Cohen-Hillel
authors: Ilana
authors: I
authors: Yron
authors: Tsipi
authors: T
authors: Meshel
authors: Adit
authors: A
authors: Ben-Baruch
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D006801:Humans; D016209:Interleukin-8 / Q000502:physiology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010641:Phenotype; D010766:Phosphorylation; D023062:Receptors, Interleukin-8A / Q000502:physiology; D023063:Receptors, Interleukin-8B / Q000502:physiology
chemical_list: D016209:Interleukin-8; D019384:Nucleic Acid Synthesis Inhibitors; D023062:Receptors, Interleukin-8A; D023063:Receptors, Interleukin-8B; D015638:Cytochalasin D; D051416:Focal Adhesion Protein-Tyrosine Kinases