title: Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK).
abstract: The tight junctions (TJs), characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK) cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK). AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedial Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Xiao Xiao
authors.initials: XX
authors.lastname: Tang
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Sidney
authors.initials: S
authors.lastname: Yu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D004285:Dogs; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D019108:Tight Junctions / Q000201:enzymology / Q000378:metabolism*
chemical_list: D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases
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