Involvement of the MAPK and RhoA/ROCK pathways in PGE2-mediated CCR7-dependent monocyte migration

Immunol Lett. 2012 Aug 30;146(1-2):70-3. doi: 10.1016/j.imlet.2012.05.002. Epub 2012 May 29.

Abstract

Prostaglandin E(2) (PGE(2)) induces the expression of C-C chemokine receptor type 7 (CCR7) on human monocytes, thereby enabling their subsequent migration in response to CCL19 and CCL21, the natural ligands for CCR7. To date, important mediators of PGE(2)-mediated monocyte migration remain unknown. In this study, we explored the role of mitogen-activated protein kinases and the RhoA/Rho-associated protein kinase (ROCK) pathway in CCR7-dependent monocyte migration in the presence of PGE(2). Our results indicate that CCL19 binding to CCR7 promotes the activation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase and leads to monocyte migration. Moreover, the RhoA/ROCK pathway was essential for PGE(2)-mediated CCR7-dependent monocyte migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Chemokine CCL19 / genetics
  • Chemokine CCL19 / immunology
  • Dinoprostone / pharmacology*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / immunology
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / immunology
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / immunology
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Primary Cell Culture
  • Receptors, CCR7 / genetics*
  • Receptors, CCR7 / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / immunology
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / immunology
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / immunology

Substances

  • CCL19 protein, human
  • CCR7 protein, human
  • Chemokine CCL19
  • Receptors, CCR7
  • RHOA protein, human
  • rho-Associated Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • rhoA GTP-Binding Protein
  • Dinoprostone