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Int. J. Mol. Sci. 2012, 13(8), 9785-9797; doi:10.3390/ijms13089785
Article

The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model

1,2,3,* , 1
,
1
 and
1
1 Department of Medicine, National Jewish Health, Denver, CO 80206, USA 2 Department of Biopharmaceutical Sciences, College of Pharmacy, Roosevelt University, Schaumburg Campus, Schaumburg, IL 60173, USA 3 Department of Medicine, University of Colorado Health Science Center, Aurora, CO 80045, USA
* Author to whom correspondence should be addressed.
Received: 14 June 2012 / Revised: 13 July 2012 / Accepted: 26 July 2012 / Published: 6 August 2012
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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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 OVA323-339-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 OVA323-339 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 OVA323-339 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; dendritic cells; Th2 cells; asthma; inflammation MnTE-2-PyP; OVA; dendritic cells; Th2 cells; asthma; inflammation
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Jungsuwadee, P.; Weaver, M.R.; Gally, F.; Oberley-Deegan, R.E. The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model. Int. J. Mol. Sci. 2012, 13, 9785-9797.

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