Format

Send to

Choose Destination
Int Immunopharmacol. 2005 Mar;5(3):495-502.

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

Author information

1
Department of Pharmacology, Faculty of Medicine, National University of Singapore, MD2 18 Medical Drive, 117597 Singapore.

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.

PMID:
15683846
DOI:
10.1016/j.intimp.2004.10.015
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center