title: The metalloporphyrin antioxidant, MnTE-2-PyP, inhibits Th2 cell immune responses in an asthma model.
abstract: MnTE-2-PyP, a superoxide dismutase mimetic, inhibited OVA-induced airway inflammation in mice suggesting an effect on Th2 responsiveness. Thus, we hypothesized that MnTE-2-PyP may alter dendritic cell-Th2 interactions. Bone marrow derived dendritic cells (DC) and OVA(323-339)-specific Th2 cells were cultured separately in the presence or absence of MnTE-2-PyP for 3 days prior to the co-culturing of the two cell types in the presence of an OVA(323-339) peptide and in some cases stimulated with CD3/CD28. MnTE-2-PyP-pretreated DC inhibited IL-4, IL-5 and IFNγ production and inhibited Th2 cell proliferation in the DC-Th2 co-culturing system in the presence of the OVA(323-339) peptide. Similar results were obtained using the CD3/CD28 cell-activation system; the addition of MnTE-2-PyP inhibited Th2 cell proliferation. MnTE-2-PyP suppressed CD25 expression on OVA-specific Th2 cells, which implied that MnTE-2-PyP can inhibit the activation of Th2 cells. MnTE-2-PyP also down-regulated co-stimulatory molecules: CD40, CD80 and CD86 on immature DC. Our studies suggest that the major mechanism by which MnTE-2-PyP inhibits airway inflammation is by acting on the DC and suppressing Th2 cell proliferation and activation.
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.|Department of Biopharmaceutical Sciences, College of Pharmacy, Roosevelt University, Schaumburg Campus, Schaumburg, IL 60173, USA.|Department of Medicine, University of Colorado Health Science Center, Aurora, CO 80045, USA.
authors.forename: Paiboon
authors.initials: P
authors.lastname: Jungsuwadee
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Weaver
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Gally
authors.affiliation: Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Oberley-Deegan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000494:pharmacology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D000975:Antioxidants; D008665:Metalloporphyrins; C520506:manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin; D010047:Ovalbumin