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    PPAR gamma AND eNOS CONTRIBUTE TO THE RESOLUTION OF CHRONIC INFLAMMATION.

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    Genre
    Thesis/Dissertation
    Date
    2011
    Author
    Evans, Kyle William
    Advisor
    Chan, Marion M.
    Committee member
    Fong, Dunne
    Eisenstein, Toby K.
    Piggot, Patrick
    Yang, Xiao-Feng
    Ashby, Barrie
    Department
    Microbiology and Immunology
    Subject
    Biology
    Enos
    Inflammation
    Ppargamma
    Resolution
    Rheumatoid Arthritis
    Permanent link to this record
    http://hdl.handle.net/20.500.12613/1179
    
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    DOI
    http://dx.doi.org/10.34944/dspace/1161
    Abstract
    Chronic inflammation follows defined phases of induction, inflammation, and resolution. The resolution phase requires cycloxygenase-2 (COX-2) activity. This study aims to address what other molecules are required for a functional resolution phase. We demonstrated that in murine collagen-induced arthritis the transcription factor, PPARgamma plays a role in the resolution phase. Inhibition of COX-2 activity results in fewer PPARgamma positive cells in the arthritic synovium. Treatment with a PPARgamma antagonist, SR202, alone, also disrupts the process of resolution. PPARgamma antagonist treatment results in a decrease in eNOS phosphorylation within the arthritic synovium. These observations indicate that PPARgamma may function to regulate eNOS activity. The source of pro-resolving nitric oxide is eNOS but not, iNOS. The effect of COX-2 inhibition on the resolution phase is ameliorated by injection of a PGE2 analog. Restoration of PGE2 levels results in an increase in PPARgamma positive cells in the arthritic synovium which correlates with this restoration of resolution. Thus, this study provides in vivo evidence for the pro-resolving role of PPARgamma and its relationship with PGE2 and eNOS.
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