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.