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Role of cyclophilins in acute allergic asthma
Author(s) -
Balsley Molly Ann,
Morton Russell A,
Okwumabua Ifeanyi,
Bukrinsky Michael I,
Constant Stephanie L
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1072.11
Subject(s) - extracellular , inflammation , chemotaxis , immunology , asthma , allergic inflammation , medicine , effector , biology , microbiology and biotechnology , receptor
Cyclophilins can function extracellularly as chemotactic agents for leukocytes. Elevated levels of extracellular cyclophilins have been observed in many inflammatory diseases. Previous studies in our laboratory suggest that extracellular cyclophilins contribute to asthmatic lung inflammation, although the mechanism of contribution is unknown. The objectives of the current study were to establish: (1) the cell source of extracellular cyclophilins and when they play a role in inflammation, (2) the impact of blocking cyclophilins using NIM811 (Novartis), a non‐immunosuppressive form of cyclosporine A, and (3) the mechanism(s) by which cyclophilins contribute to inflammation. Using a mouse model of acute allergic asthma, elevated levels of cyclophilins were observed throughout the asthmatic response, potentially from infiltrating leukocytes. NIM811 treatment resulted in a 30–50% reduction in numbers of eosinophils and effector CD4 + T cells within lung tissues and airways, suggesting that extracellular cyclophilins function by promoting leukocyte recruitment. Blocking extracellular cyclophilins may provide a novel approach for reducing the pathology associated with allergic asthma. Funded by NIH AI‐059208.