title: TLR2 regulates gap junction intercellular communication in airway cells.
abstract: The innate immune response to inhaled bacteria, such as the opportunist Pseudomonas aeruginosa, is initiated by TLR2 displayed on the apical surface of airway epithelial cells. Activation of TLR2 is accompanied by an immediate Ca(2+) flux that is both necessary and sufficient to stimulate NF-kappaB and MAPK proinflammatory signaling to recruit and activate polymorphonuclear leukocytes in the airway. In human airway cells, gap junction channels were found to provide a regulated conduit for the movement of Ca(2+) from cell to cell. In response to TLR2 stimulation, by either lipid agonists or P. aeruginosa, gap junctions functioned to transiently amplify proinflammatory signaling by communicating Ca(2+) fluxes from stimulated to adjacent, nonstimulated cells thus increasing epithelial CXCL8 production. P. aeruginosa stimulation also induced tyrosine phosphorylation of connexin 43 and association with c-Src, events linked to the closure of these channels. By 4 h postbacterial stimulation, gap junction communication was decreased indicating an autoregulatory control of the connexins. Thus, gap junction channels comprised of connexin 43 and other connexins in airway cells provide a mechanism to coordinate and regulate the epithelial immune response even in the absence of signals from the immune system.
authors: Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
authors: Francis J
authors: FJ
authors: Martin
authors: Alice S
authors: AS
authors: Prince
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D002460:Cell Line; D017630:Connexins / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D012137:Respiratory System / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D017630:Connexins; D016207:Cytokines; D051195:Toll-Like Receptor 2; D002118:Calcium