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: Paiboon Jungsuwadee, Michael R Weaver, Fabienne Gally, Rebecca E Oberley-Deegan
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 13 Issue 8 Pg. 9785-9797 ( 2012) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 22949830 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• Metalloporphyrins
• manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin
• Ovalbumin

Topics

• Animals
• Antioxidants (pharmacology)
• Asthma (drug therapy, immunology, pathology)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Dendritic Cells (cytology, drug effects, immunology)
• Disease Models, Animal
• Flow Cytometry
• Metalloporphyrins (pharmacology)
• Mice
• Mice, Inbred BALB C
• Ovalbumin (pharmacology)
• Th2 Cells (drug effects, immunology, pathology)