PGE2-induced metalloproteinase-9 is essential for dendritic cell migration.
Following antigen acquisition and maturation, dendritic cells (DCs) disengage from the extracellular matrix, cross basement membranes, and travel to draining lymph nodes to activate T cells. CCR7 expression is necessary but not sufficient for the directional migration of DCs. Prostaglandin E2 (PGE2), present in inflammatory sites, induces DC migration, presumably by enacting a migration-permissive gene expression program. Since regulation of DC migration is highly important for their use in vaccination and therapy, we examined the PGE2-induced changes in the expression of metalloproteinases (MMPs). Our results indicate that PGE2 significantly up-regulates MMP-9 expression, induces both secreted and membrane-bound MMP-9, and that in turn, DC-derived MMP-9 is essential for DC chemotaxis in response to the CCR7 ligand CCL19, Matrigel migration, and in vivo migration in both wild-type and MMP-9-deficient hosts. We conclude that DCs matured within inflammatory sites require both CCR7 and PGE2-induced MMP-9 for their directional migration to draining lymph nodes.
Yen
Jui-Hung
JH
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Khayrullina
Tanzilya
T
Ganea
Doina
D
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D054415:Chemokine CCL19 / Q000378:metabolism; D003094:Collagen; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000201:enzymology*; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D004338:Drug Combinations; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D007797:Laminin; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D011509:Proteoglycans; D012333:RNA, Messenger / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D054415:Chemokine CCL19; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C545645:Ptger2 protein, mouse; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D014409:Tumor Necrosis Factor-alpha; C059485:matrigel; D007371:Interferon-gamma; D003094:Collagen; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone