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Effects of proteasome inhibition by a novel imidazoline on ovalbumin‐induced airway inflammation and hyperresponsiveness
Author(s) -
Azevedo Lauren,
Proper Steven,
Greenwood Krista,
Jackson-Humbles Daven,
Bramble Lori,
Harkema Jack,
Wagner James,
Tepe Jetze
Publication year - 2012
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.26.1_supplement.669.7
Subject(s) - ovalbumin , inflammation , immunology , medicine , airway resistance , airway hyperresponsiveness , bronchial hyperresponsiveness , pharmacology , lung , chemistry , asthma , respiratory disease , immune system
Activation of nuclear factor‐ κB (NF‐ κB) has been linked to pulmonary inflammation and airway hyperresponsiveness. In previous studies we demonstrated that proteasome inhibition by a novel imidazoline (TCH‐013) inhibits NF‐ κB activation. To further characterize the role of the proteasome and NF‐ κB, we administered TCH‐013 during the effector phase of allergic airway disease. BALB/cJ mice were sensitized to ovalbumin (OVA) on Day 0, and boosted with OVA on Day 10. Mice were treated with TCH‐013 (i.p. 50mg/kg or vehicle) 1 hour prior to each OVA challenge on Days 17, 18 and 19. On Day 21, alterations in lung resistance and pulmonary inflammation were assessed. Treatment with TCH‐013 attenuated OVA‐induced increases in BALF total cellularity, eosinophils, and lymphocytes. Ovalbumin sensitized animals also exhibited increased IL‐5, IL‐6, IL‐13, KC, and airway resistance. These parameters were not affected by TCH‐013 administration. Proteasome inhibition by a TCH‐013 attenuated ovalbumin‐induced pulmonary inflammation but not airway hyperresponsiveness. We gratefully acknowledge support from Michigan State University and NIH (5R01CA142644).