Involvement of the MAPK and RhoA/ROCK pathways in PGE2-mediated CCR7-dependent monocyte migration.
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.
Département de Biologie, Faculté des Sciences, Université de Sherbrooke, Sherbrooke (QC), Canada J1K 2R1.
Marc-André
MA
Allaire
Nancy
N
Dumais
D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D054415:Chemokine CCL19 / Q000235:genetics / Q000276:immunology; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000276:immunology; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D061251:Primary Cell Culture; D054400:Receptors, CCR7 / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology; D054460:rho-Associated Kinases / Q000235:genetics / Q000276:immunology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000276:immunology
C515460:CCL19 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054400:Receptors, CCR7; C066737:RHOA protein, human; D054460:rho-Associated Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein; D015232:Dinoprostone