Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation

Aich, Jyotirmoi ; Mabalirajan, Ulaganathan ; Ahmad, Tanveer ; Agrawal, Anurag ; Ghosh, Balaram (2012) Loss-of-function of inositol polyphosphate-4-phosphatase reversibly increases the severity of allergic airway inflammation Nature Communications, 3 . p. 877. ISSN 2041-1723

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Official URL: http://www.nature.com/ncomms/journal/v3/n6/full/nc...

Related URL: http://dx.doi.org/10.1038/ncomms1880

Abstract

Inositol polyphosphate phosphatases regulate the magnitude of phosphoinositide-3 kinase signalling output. Although inositol polyphosphate-4-phosphatase is known to regulate phosphoinositide-3 kinase signalling, little is known regarding its role in asthma pathogenesis. Here we show that modulation of inositol polyphosphate-4-phosphatase alters the severity of asthma. Allergic airway inflammation in mice led to calpain-mediated degradation of inositol polyphosphate-4-phosphatase. In allergic airway inflammation models, preventing inositol polyphosphate-4-phosphatase degradation by inhibiting calpain activity, or overexpression of inositol polyphosphate-4-phosphatase in mouse lungs, led to attenuation of the asthma phenotype. Conversely, knockdown of inositol polyphosphate-4-phosphatase severely aggravated the allergic airway inflammation and the asthma phenotype. Interestingly, inositol polyphosphate-4-phosphatase knockdown in lungs of naive mice led to spontaneous airway hyper-responsiveness, suggesting that inositol polyphosphate-4-phosphatase could be vital in maintaining the lung homeostasis. We suggest that inositol polyphosphate-4-phosphatase has an important role in modulating inflammatory response in asthma, and thus, uncover a new understanding of the complex interplay between inositol signalling and asthma, which could provide alternative strategies in asthma management.

Item Type:Article
Source:Copyright of this article belongs to Nature Publishing Group.
ID Code:96395
Deposited On:18 Dec 2012 06:52
Last Modified:18 Dec 2012 06:52

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