Prostaglandin E2 inhibits production of the inflammatory chemokines CCL3 and CCL4 in dendritic cells.
Dendritic cells bridge innate and adaptive immunity and participate in both responses. Upon capture of pathogens, dendritic cells release inflammatory cytokines and chemokines, attracting other immune cells to the infection site. Anti-inflammatory cytokines, glucocorticoids, anti-inflammatory neuropeptides, and lipid mediators such as prostaglandin E2 (PGE2) limit and control the inflammatory response. In this study we report that exogenous PGE2 inhibits CCL3 (MIP-1alpha) and CCL4 (MIP-1beta) expression and release from dendritic cells stimulated with either lipopolysaccharide (LPS), a TLR4 ligand, or peptidoglycan, a TLR2 ligand. The inhibition is dose-dependent and occurs at both the mRNA and protein levels. The inhibitory effect is mediated through EP2 and EP4 receptors and requires the presence of PGE2 at the time of LPS stimulation. Intraperitoneal administration of PGE2 together with LPS results in a reduction in the levels of CCL3 and CCL4 released in the peritoneal fluid, a reduction in the number of dendritic cells accumulating in the peritoneal cavity, and a reduction in CCL3 amount per cell in the peritoneal cell population. These results suggest that one of the mechanisms by which endogenous PGE2 acts as an anti-inflammatory agent, is the inhibition of inflammatory chemokine release from activated dendritic cells, preventing the excess accumulation of activated immune cells.
Jing
Huie
H
Department of Biological Sciences, Rutgers University, Newark, NJ 07102, USA.
Vassiliou
Evros
E
Ganea
Doina
D
D000818:Animals; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D015232:Dinoprostone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D016133:Polymerase Chain Reaction; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000235:genetics*
C515355:Ccr4 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D015232:Dinoprostone