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The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model
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
* Author to whom correspondence should be addressed.
Received: 14 June 2012; in revised form: 13 July 2012 / Accepted: 26 July 2012 / Published: 6 August 2012
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
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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.
Jungsuwadee P, Weaver MR, Gally F, Oberley-Deegan RE. The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model. International Journal of Molecular Sciences. 2012; 13(8):9785-9797.
Jungsuwadee, Paiboon; Weaver, Michael R.; Gally, Fabienne; Oberley-Deegan, Rebecca E. 2012. "The Metalloporphyrin Antioxidant, MnTE-2-PyP, Inhibits Th2 Cell Immune Responses in an Asthma Model." Int. J. Mol. Sci. 13, no. 8: 9785-9797.