Phosphoinositide 3-kinase-δ inhibitor reduces vascular permeability in a murine model of asthma Kyung Sun Lee, PhD, Seoung Ju Park, MD, So Ri Kim, MD,

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Presentation transcript:

Phosphoinositide 3-kinase-δ inhibitor reduces vascular permeability in a murine model of asthma Kyung Sun Lee, PhD, Seoung Ju Park, MD, So Ri Kim, MD, Kyung Hoon Min, MD, Sun Mi Jin, BS, Kamal D. Puri, PhD, Yong Chul Lee, MD, PhD Journal of Allergy and Clinical Immunology Volume 118, Issue 2, Pages 403-409 (August 2006) DOI: 10.1016/j.jaci.2006.04.041 Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 1 Effect of IC87114, SU5614, or SU1498 on VEGF protein expression. Sampling was performed at 72 hours after the last challenge in saline-inhaled mice administered saline (SAL+SAL), ovalbumin (OVA)-inhaled mice administered saline (OVA+SAL), OVA-inhaled mice administered drug vehicle (OVA+VEH), OVA-inhaled mice administered 0.1 mg/kg of IC87114 (OVA+IC87114 0.1 mg/kg), OVA-inhaled mice administered 1 mg/kg of IC87114 (OVA+IC87114 1.0 mg/kg), OVA-inhaled mice administered SU5614 (OVA+SU5614), or OVA-inhaled mice administered SU1498 (OVA+SU1498). A, Western blotting of VEGF in lung tissues. B, Densitometric analyses are presented as the relative ratio of VEGF to actin. The relative ratio of VEGF in the lung tissues of SAL+SAL is arbitrarily presented as 1. C, Enzyme immunoassay of VEGF in BAL fluids. Bars represent means ± SEMs from 8 mice per group. #P < .05 vs SAL+SAL; ∗P < .05 vs OVA+SAL. Journal of Allergy and Clinical Immunology 2006 118, 403-409DOI: (10.1016/j.jaci.2006.04.041) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 2 Localization of immunoreactive VEGF. Sampling was performed at 72 hours after the last challenge in BAL fluids from sensitized mice challenged with saline (A), from sensitized mice challenged with ovalbumin (B), from ovalbumin-inhaled mice administered 0.1 mg/kg of IC87114 (C), and from ovalbumin-inhaled mice administered 1 mg/kg of IC87114 (D). Brown indicates VEGF+ cells. Bars indicate scale of 50 μm. Journal of Allergy and Clinical Immunology 2006 118, 403-409DOI: (10.1016/j.jaci.2006.04.041) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 3 Effect of IC87114, SU5614, or SU1498 on plasma exudation. Bars represent means ± SEMs from 8 mice per group. #P < .05 vs saline (SAL) +SAL; ∗P < .05 vs ovalbumin (OVA) +SAL. Journal of Allergy and Clinical Immunology 2006 118, 403-409DOI: (10.1016/j.jaci.2006.04.041) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 4 Effect of IC87114 on HIF-1α and HIF-1β expression in nuclear protein extracts from lung tissues. A, HIF-1α and HIF-1β expression in nuclear protein extracts from lung tissues. B, Densitometric analyses are presented as the relative ratio of HIF-1α to HIF-1β. The relative ratio of HIF-1α in the lung tissues of saline (SAL) +SAL is arbitrarily presented as 1. Bars represent means ± SEMs from 8 mice per group. #P < .05 vs SAL+SAL; ∗P < .05 vs ovalbumin (OVA) +SAL. VEH, Vehicle. Journal of Allergy and Clinical Immunology 2006 118, 403-409DOI: (10.1016/j.jaci.2006.04.041) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions

Fig 5 Effect of IC87114, SU5614, or SU1498 on total cells and differential cellular components of BAL fluids (A) and airway responsiveness (B) of ovalbumin (OVA)-sensitized and ovalbumin-challenged mice. A, The numbers of each cellular component of BAL were counted at 72 hours after the last challenge. B, Airway responsiveness was measured at 72 hours after the last challenge as described in Methods. Bars represent means ± SEMs from 8 mice per group. #P < .05 vs saline (SAL)+SAL; ∗P < .05 vs OVA+SAL. VEH, Vehicle. Journal of Allergy and Clinical Immunology 2006 118, 403-409DOI: (10.1016/j.jaci.2006.04.041) Copyright © 2006 American Academy of Allergy, Asthma and Immunology Terms and Conditions