TY - JOUR T1 - LSC 2014 abstract - The cation channel TRPV4 regulates epithelial barrier responses to lipopolysaccharides JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P3891 AU - Yeranddy Alpizar AU - Brett Boonen AU - Katrien Luyts AU - Vanessa De Vooght AU - Benoit Nemery AU - Peter Hoet AU - Karel Talavera Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P3891.abstract N2 - TRPV4 is a Ca2+-permeable non-selective cation channel belonging to the vanilloid subfamily of Transient Receptor Potential proteins. This channel has a rather ubiquitous expression in epithelial cells (skin, airways, endothelium and urothelium) and it is activated by a wide variety of physical and chemical stimuli, including heat, arachidonic acid metabolites, endocannabinoids and synthetic α-phorbol derivatives. In bronchial epithelial cells (16HBE), we found that TRPV4 is directly activated by lipopolysaccharides (LPS), through a TLR4-independent mechanism. In these cells, TRPV4-mediated calcium influx was followed by a release of nitric oxide (NO) from constitutively expressed inducible nitric oxide synthases (iNOS). TRPV4 activation by LPS induces an increase in iNOS enzymatic activity by promoting iNOS disaggregation from inactive cytoplasmic iNOS aggresomes. On the other hand, acute stimulation of TRPV4 induced a rapid increase of the transepithelial electrical resistance. LPS induced a TRPV4-dependent migration of the ZO-1 adaptor protein from the cytoplasm to the plasma membrane and the structural reorganization of occludin and claudin-2 at the tight junctions. Thus, TRPV4 emerges as a novel player in innate immune responses, conferring epithelial cells the ability to quickly respond to LPS challenge through mechanisms that reach far beyond a merely passive role as physical barrier. ER -