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Title: An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model
Authors: Duan, W.
Aguinaldo, Datiles A.M.K.
Wong, W.S.F. 
Leung, B.P.
Vlahos, C.J.
Keywords: Airway hyperresponsiveness
Mucus hypersecretion
Issue Date: 2005
Source: Duan, W., Aguinaldo, Datiles A.M.K., Wong, W.S.F., Leung, B.P., Vlahos, C.J. (2005). An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model. International Immunopharmacology 5 (3) : 495-502. ScholarBank@NUS Repository.
Abstract: Phosphoinositide 3-kinase (PI3K) exhibits broad functional effects in immune cells. We investigated the role of PI3K in allergic airway inflammation using LY294002, a specific PI3K inhibitor, in a mouse asthma model. BALB/c mice were sensitized and challenged with ovalbumin (OVA), and developed airway eosinophilia, mucus hypersecretion, elevation in cytokine levels, and airway hyperresponsiveness. Intratracheal administration of LY294002 significantly inhibited OVA-induced increases in total cell counts, eosinophil counts, and IL-5, IL-13, and eotaxin levels in bronchoalveolar lavage fluid. Histological studies show that LY294002 dramatically inhibited OVA-induced lung tissue eosinophilia and airway mucus production. In addition, LY294002 significantly suppressed OVA-induced airway hyperresponsiveness to inhaled methacholine. Western blot analysis of whole lung lysates shows that LY294002 markedly attenuated OVA-induced serine phosphorylation of Akt, a direct downstream substrate of PI3K. Taken together, our findings suggest that inhibition of PI3K signaling pathway can suppress T-helper type 2 (Th2) cytokine production, eosinophil infiltration, mucus production, and airway hyperresponsiveness in a mouse asthma model and may have therapeutic potential for the treatment of allergic airway inflammation. © 2004 Elsevier B.V. All rights reserved.
Source Title: International Immunopharmacology
ISSN: 15675769
DOI: 10.1016/j.intimp.2004.10.015
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