title: Macrophage inflammatory protein-3 beta enhances IL-10 production by activated human peripheral blood monocytes and T cells.
abstract: We report that the addition of human macrophage inflammatory protein-3 beta (MIP-3 beta) to cultures of human PBMCs that have been activated with LPS or PHA results in a significant enhancement of IL-10 production. This effect was concentration-dependent, with optimal MIP-3 beta concentrations inducing more than a 5-fold induction of IL-10 from LPS-stimulated PBMCs and a 2- to 3-fold induction of IL-10 from PHA-stimulated PBMCs. In contrast, no significant effect on IL-10 production was observed when 6Ckine, the other reported ligand for human CCR7, or other CC chemokines such as monocyte chemoattractant protein-1, RANTES, MIP-1 alpha, and MIP-1 beta were added to LPS- or PHA-stimulated PBMCs. Similar results were observed using activated purified human peripheral blood monocytes or T cells. Addition of MIP-3 beta to nonactivated PBMCs had no effect on cytokine production. Enhancement of IL-10 production by MIP-3beta correlated with the inhibition of IL-12 p40 and TNF-alpha production by monocytes and with the impairment of IFN-gamma production by T cells, which was reversed by addition of anti-IL-10 Abs to the cultures. The ability of MIP-3 beta to augment IL-10 production correlated with CCR7 mRNA expression and stimulation of intracellular calcium mobilization in both monocytes and T cells. These data indicate that MIP-3 beta acts directly on human monocytes and T cells and suggest that this chemokine is unique among ligands binding to CC receptors due to its ability to modulate inflammatory activity via the enhanced production of the anti-inflammatory cytokine IL-10.
authors.affiliation: Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
authors.forename: H D
authors.initials: HD
authors.lastname: Byrnes
authors.forename: H
authors.initials: H
authors.lastname: Kaminski
authors.forename: A
authors.initials: A
authors.lastname: Mirza
authors.forename: G
authors.initials: G
authors.lastname: Deno
authors.forename: D
authors.initials: D
authors.lastname: Lundell
authors.forename: J S
authors.initials: JS
authors.lastname: Fine
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology*; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000502:physiology*; D016207:Cytokines / Q000037:antagonists & inhibitors; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; C515460:CCL19 protein, human; C515478:CCL21 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D016207:Cytokines; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D016753:Interleukin-10