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Phosphoinositide 3-kinase {delta} inhibitor suppresses IL-17 expression in a murine asthma model.

Authors: Park, SJ  Lee, KS  Kim, SR  Min, KH  Moon, H  Lee, MH  Chung, CR  Han, HJ  Puri, KD  Lee, YC 
Citation: Park SJ, etal., Eur Respir J. 2010 Mar 29.
Pubmed: (View Article at PubMed) PMID:20351038
DOI: Full-text: DOI:10.1183/09031936.00106609

Phosphoinositide 3-kinases (PI3Ks) contribute to the pathogenesis of asthma by regulating the activation of inflammatory mediators, inflammatory cell recruitment, and immune cell function. Recent findings have indicated that PI3Ks also regulate the expression of interleukin (IL)-17, which has been introduced as an important cytokine involved in airway inflammation.In the present study, we investigated a role of PI3Kdelta in the regulation of IL-17 expression in allergic airway disease using a murine model of asthma.After ovalbumin (OVA) inhalation, administration of a selective p110delta inhibitor, IC87114, significantly attenuated airway infiltration of total cells, lymphocytes, neutrophils, and eosinophils as well as airway hyperresponsiveness and decreased the increase in IL-17 protein and mRNA expression. Moreover, IC87114 reduced levels of IL-4, IL-5, and IL-13, expression of keratinocyte chemoattractant protein and mRNA, and nuclear factor-kappaB (NF-kappaB) activity. In addition, a NF-kappaB inhibitor, BAY 11-7085 substantially reduced the increase in IL-17 protein levels. Our results also showed that inhibition of IL-17 activity with an anti-IL-17 antibody remarkably reduced airway inflammation and hyperresponsiveness.These findings suggest that inhibition of the p110delta signalling pathway suppresses IL-17 expression through regulation of NF-kappaB activity and thus has therapeutic potential in asthma.

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CRRD Object Information
CRRD ID: 4888527
Created: 2010-11-23
Species: All species
Last Modified: 2010-11-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.