An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model.

作者: Wei Duan , Ana M.K. Aguinaldo Datiles , Bernard P. Leung , Chris J. Vlahos , W.S. Fred Wong

DOI: 10.1016/J.INTIMP.2004.10.015

关键词:

摘要: Phosphoinositide 3-kinase (PI3K) exhibits broad functional effects in immune cells. We investigated the role of PI3K allergic airway inflammation using LY294002, a specific inhibitor, mouse asthma model. BALB/c mice were sensitized and challenged with ovalbumin (OVA), developed eosinophilia, mucus hypersecretion, elevation cytokine levels, hyperresponsiveness. Intratracheal administration LY294002 significantly inhibited OVA-induced increases total cell counts, eosinophil IL-5, IL-13, eotaxin levels bronchoalveolar lavage fluid. Histological studies show that dramatically lung tissue eosinophilia production. In addition, suppressed hyperresponsiveness to inhaled methacholine. Western blot analysis whole lysates shows markedly attenuated serine phosphorylation Akt, direct downstream substrate PI3K. Taken together, our findings suggest inhibition signaling pathway can suppress T-helper type 2 (Th2) production, infiltration, model may have therapeutic potential for treatment inflammation.

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