title: Prostaglandin I2 analogs inhibit proinflammatory cytokine production and T cell stimulatory function of dendritic cells.
abstract: Signaling through the PGI(2) receptor (IP) has been shown to inhibit inflammatory responses in mouse models of respiratory syncytial viral infection and OVA-induced allergic responses. However, little is known about the cell types that mediate the anti-inflammatory function of PGI(2.) In this study, we determined that PGI(2) analogs modulate dendritic cell (DC) cytokine production, maturation, and function. We report that PGI(2) analogs (iloprost, cicaprost, treprostinil) differentially modulate the response of murine bone marrow-derived DC (BMDC) to LPS in an IP-dependent manner. The PGI(2) analogs decreased BMDC production of proinflammatory cytokines (IL-12, TNF-alpha, IL-1alpha, IL-6) and chemokines (MIP-1alpha, MCP-1) and increased the production of the anti-inflammatory cytokine IL-10 by BMDCs. The modulatory effect was associated with IP-dependent up-regulation of intracellular cAMP and down-regulation of NF-kappaB activity. Iloprost and cicaprost also suppressed LPS-induced expression of CD86, CD40, and MHC class II molecules by BMDCs and inhibited the ability of BMDCs to stimulate Ag-specific CD4 T cell proliferation and production of IL-5 and IL-13. These findings suggest that PGI(2) signaling through the IP may exert anti-inflammatory effects by acting on DC.
authors.affiliation: Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. weisong.zhou@vanderbilt.edu
authors.forename: Weisong
authors.initials: W
authors.lastname: Zhou
authors.forename: Koichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Kasia
authors.initials: K
authors.lastname: Goleniewska
authors.forename: Jamye F
authors.initials: JF
authors.lastname: O'Neal
authors.forename: Shaoquan
authors.initials: S
authors.lastname: Ji
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Blackwell
authors.forename: Garret A
authors.initials: GA
authors.lastname: Fitzgerald
authors.forename: Karine M
authors.initials: KM
authors.lastname: Egan
authors.forename: Mark W
authors.initials: MW
authors.lastname: Geraci
authors.forename: R Stokes
authors.initials: RS
authors.lastname: Peebles
mesh_terms: D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000172:deficiency / Q000378:metabolism / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*
chemical_list: D051940:B7-2 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D016328:NF-kappa B; D011464:Epoprostenol; D000242:Cyclic AMP