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This Article Full Text Full Text (PDF) All Versions of this Article: 296/3/L328    most recent 90431.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kalari, S. Articles by Natarajan, V. Search for Related Content PubMed PubMed Citation Articles by Kalari, S. Articles by Natarajan, V.

Role of acylglycerol kinase in LPA-induced IL-8 secretion and transactivation of epidermal growth factor-receptor in human bronchial epithelial cells

¹Department of Medicine, Section of Pulmonary and Critical Care Medicine, ²The University of Chicago, Chicago, Illinois

Submitted 6 August 2008 ; accepted in final form 15 December 2008

LPA (lysophosphatidic acid) is a potent bioactive phospholipid, which regulates a number of diverse cellular responses through G protein-coupled LPA receptors. Intracellular LPA is generated by the phosphorylation of monoacylglycerol by acylglycerol kinase (AGK); however, the role of intracellular LPA in signaling and cellular responses remains to be elucidated. Here, we investigated signaling pathways of IL-8 secretion mediated by AGK and intracellular LPA in human bronchial epithelial cells (HBEpCs). Expression of AGK in HBEpCs was detected by real-time PCR, and overexpressed AGK was mainly localized in mitochondria as determined by immunofluorescence and confocal microscopy. Overexpression of lentiviral AGK wild type increased intracellular LPA production (1.8-fold), enhanced LPA-mediated IL-8 secretion, and stimulated tyrosine phosphorylation epidermal growth factor-receptor (EGF-R). Furthermore, downregulation of native AGK by AGK small interfering RNA decreased intracellular LPA levels (2-fold) and attenuated LPA-induced p38 MAPK, JNK, and NF-B activation, tyrosine phosphorylation of EGF-R, and IL-8 secretion. These results suggest that native AGK regulates LPA-mediated IL-8 secretion involving MAPKs, NF-B, and transactivation of EGF-R. Thus AGK may play an important role in innate immunity and airway remodeling during inflammation.

lysophosphatidic acid; signal transduction; MAPKs; NF-B