HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Martin, F. J. Articles by Prince, A. S. Search for Related Content PubMed PubMed Citation Articles by Martin, F. J. Articles by Prince, A. S.

TLR2 Regulates Gap Junction Intercellular Communication in Airway Cells¹

Francis J. Martin^* and Alice S. Prince^2,*,

^* Department of Pharmacology and Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY 10032

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 Ca²⁺ flux that is both necessary and sufficient to stimulate NF-B 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 Ca²⁺ 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 Ca²⁺ 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant R01 HL073989 (to A.S.P.).

² Address correspondence and reprint requests to Dr. Alice S. Prince, Columbia University, Black Building 416, 650 West 168th Street, New York, NY 10032. E-mail address: asp7{at}columbia.edu

³ Abbreviations used in this paper: PMN, polymorphonuclear leukocyte; Cx43, connexin 43; Cx26, connexin 26; Cx32, connexin 32; P3C, Pam₃Cys-Ser-Lys₄; siRNA, small-interfering RNA; ZO-1, zona occludens-1; CF, cystic fibrosis.

⁴ The online version of this article contains supplemental material.

This article has been cited by other articles:

				C. Beisswenger, E. S. Lysenko, and J. N. Weiser Early Bacterial Colonization Induces Toll-Like Receptor-Dependent Transforming Growth Factor {beta} Signaling in the Epithelium Infect. Immun., May 1, 2009; 77(5): 2212 - 2220. [Abstract] [Full Text] [PDF]