Secretory Inositol Polyphosphate 4-Phosphatase Protects Against Airway Inflammation and Remodeling.

Authors: Khanna K, Chaudhuri R, Aich J, Pattnaik B, Panda L, Prakash YS, Mabalirajan U, Ghosh B, Agrawal A Abstract The asthma candidate gene, inositol polyphosphate 4-phosphatase (INPP4A) is a lipid phosphatase that negatively regulates the phosphoinositide-3-kinase (PI3K)/Akt pathway. Destabilizing genetic variants of INPP4A increase asthma risk and lung-specific INPP4A knockdown induces asthma-like features. INPP4A is known to localise intracellularly and its extracellular presence has not been reported yet. Here we show for the first time that INPP4A is secreted by airway epithelial cells and that extracellular INPP4A critically inhibits airway inflammation and remodeling. INPP4A was present in blood and broncho-alveolar lavage fluid and this extracellular INPP4A was reduced in...

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