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Int J Mol Sci. 2012;13(8):9785-97. doi: 10.3390/ijms13089785. Epub 2012 Aug 6.

The metalloporphyrin antioxidant, MnTE-2-PyP, inhibits Th2 cell immune responses in an asthma model.

Author information

1
Department of Medicine, National Jewish Health, Denver, CO 80206, USA; E-Mails: weaverm@njhealth.org (M.R.W.); gallyf@njhealth.org (F.G.); oberleyr@njhealth.org (R.E.O.-D.).

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.

KEYWORDS:

MnTE-2-PyP; OVA; Th2 cells; asthma; dendritic cells; inflammation

PMID:
22949830
PMCID:
PMC3431828
DOI:
10.3390/ijms13089785
[Indexed for MEDLINE]
Free PMC Article

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