12/15-lipoxygenase is an interleukin-13 and interferon-γ counterregulated-mediator of allergic airway inflammation.
Interleukin-13 and interferon-γ are important effectors of T-helper cells. Interleukin-13 increases expression of the arachidonic acid-metabolizing enzyme, 15-lipoxygenase-1, in a variety of cell types. 15-lipoxygenase-1 is dramatically elevated in the airways of subjects with asthma. Studies in animals indicate that 15-lipoxygenase-1 contributes to the development of allergic airway inflammation but is protective in some other forms of inflammation. We tested the hypothesis that the ability of interleukin-13 and interferon-γ to counterregulate allergic airway inflammation was potentially mediated by counterregulation of 12/15-lipoxygenase, the mouse ortholog of 15-lipoxygenase-1. The airways of mice were treated with interleukin-13 or interferon-γ one day prior to each of the four allergen exposures. Interleukin-13 augmented and interferon-γ inhibited allergic airway inflammation independently of systemic IgE and mucosal IgA responses but in association with counterregulation of 12/15-lipoxygenase. Interleukin-13 and interferon-γ counterregulate 12/15-lipoxygenase potentially contributing to the effects of these cytokines on allergic airway inflammation.
Allergy-Immunology Division, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Alexa R
AR
Lindley
Margaret
M
Crapster-Pregont
Yanjun
Y
Liu
Douglas A
DA
Kuperman
D000485:Allergens / Q000378:metabolism; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D001249:Asthma / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity; D007070:Immunoglobulin A / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
C475064:12-15-lipoxygenase; D000485:Allergens; D016207:Cytokines; D007070:Immunoglobulin A; D018793:Interleukin-13; D007073:Immunoglobulin E; D007371:Interferon-gamma; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase