Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK).
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.
Tang
Xiao Xiao
XX
Epithelial Cell Biology Research Center, School of Biomedial Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong.
Chen
Hao
H
Yu
Sidney
S
Zhang
Li
L
Caplan
Michael J
MJ
Chan
Hsiao Chang
HC
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*
D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases
Curr Protein Pept Sci. 2008 Oct;9(5):478-92
18855699
Am J Physiol. 1998 Jan;274(1):F1-9
9458817
Mol Biol Cell. 2005 Oct;16(10):5040-52
16055505
Am J Physiol. 1992 Aug;263(2 Pt 1):C313-8
1514579
J Cell Sci. 2004 Nov 1;117(Pt 23):5509-19
15494377
Am J Physiol. 1990 Dec;259(6 Pt 1):C978-86
2124417
Am J Physiol. 1989 Aug;257(2 Pt 1):L109-15
2788366
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17272-7
17088526
Am J Respir Cell Mol Biol. 1996 Nov;15(5):624-32
8918369
Cell Metab. 2010 Jun 9;11(6):554-65
20519126
Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):819-22
17204563
Front Biosci (Landmark Ed). 2009 Jan 01;14:1902-16
19273172
Endocrinology. 2003 Dec;144(12):5179-83
12960015
J Cell Biol. 1986 Feb;102(2):457-68
3511070
Mol Cancer Ther. 2007 May;6(5):1562-71
17513605
Int J Obes (Lond). 2008 Sep;32 Suppl 4:S7-12
18719601
Nature. 2008 Jan 31;451(7178):578-82
18235500
J Cell Biol. 1978 Jun;77(3):853-80
567227
World J Gastroenterol. 2004 Jun 1;10(11):1594-9
15162532
Cell Biol Int. 2006 Dec;30(12):977-82
17011218
J Biol Chem. 2002 Feb 8;277(6):4247-54
11729192
Cell Biol Int. 2010 Sep;34(9):951-8
20557292
Cell Cycle. 2007 Nov 15;6(22):2755-9
17986859