CCR7-specific migration to CCL19 and CCL21 is induced by PGE(2) stimulation in human monocytes: Involvement of EP(2)/EP(4) receptors activation

Mol Immunol. 2009 Aug;46(13):2682-93. doi: 10.1016/j.molimm.2008.08.269. Epub 2009 Jul 9.


The recent demonstration that newly recruited monocytes do not die at the site of inflammation, but migrate to draining lymph nodes, raises the question on the mechanism involved in this process. In this study, we demonstrate for the first time that prostaglandin E(2) (PGE(2)) regulates the expression and the activity of CCR7 in human blood-isolated monocytes as well as in the MONO-MAC-1 cell lineage. PGE(2) induces intracellular cAMP formation through engagement of the E-prostanoid 2/E-prostanoid 4 (EP(2)/EP(4)) receptors present on monocytes. Migration to chemokines CCL19 and CCL21 in the PGE(2)-stimulated monocytes is mediated through the augmentation of cAMP concentration and furthermore, the cAMP/PKA pathway appears to act as the major inducer of CCR7 transcription in MONO-MAC-1. While p38 MAPK was induced by PGE(2), we observed that PGE(2) can downregulate p42/p44 MAPK phosphorylation. At the transcription level, inhibition of p38 MAPK inhibits CCR7 mRNA expression. Finally, we demonstrated that transcription factors CREB-1 and C/EBPalpha and C/EBPbeta are translocated to the nucleus following PGE(2) stimulation and bind the potent CCR7 promoter region. Our findings may have important implication for HIV-1 migration to the lymph nodes since macrophages and monocytes, particularly CD16 positive subset, are susceptible to HIV-1 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cells, Cultured
  • Chemokine CCL19 / metabolism*
  • Chemokine CCL21 / metabolism*
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Dinoprostone / pharmacology*
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Gene Expression / drug effects
  • Humans
  • Monocytes / cytology
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / metabolism*
  • Receptors, Prostaglandin E / metabolism
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors


  • CCR7 protein, human
  • Chemokine CCL19
  • Chemokine CCL21
  • Nuclear Proteins
  • PTGER2 protein, human
  • PTGER4 protein, human
  • Receptors, CCR7
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP2 Subtype
  • Receptors, Prostaglandin E, EP4 Subtype
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Dinoprostone