Gram-positive bacterial cell wall components including PGN (peptidoglycan) elicit a potent pro-inflammatory response in diverse cell types, including endothelial cells, by activating TLR2 (Toll-like receptor 2) signalling. The functional integrity of the endothelium is under the influence of a network of gap junction intercellular communication channels composed of Cxs (connexins) that also form hemichannels, signalling conduits that are implicated in ATP release and purinergic signalling. PGN modulates Cx expression in a variety of cell types, yet effects in endothelial cells remain unresolved. Using the endothelial cell line b.End5, a 6 h challenge with PGN induced IL-6 (interleukin 6), TLR2 and Cx43 mRNA expression that was associated with enhanced Cx43 protein expression and gap junction coupling. Cx43 hemichannel activity, measured by ATP release from the cells, was induced following 15 min of exposure to PGN. Inhibition of hemichannel activity with carbenoxolone or apyrase prevented induction of IL-6 and TLR2 mRNA expression by PGN, but had no effect on Cx43 mRNA expression levels. In contrast, knockdown of TLR2 expression had no effect on PGN-induced hemichannel activity, but reduced the level of TLR2 and Cx43 mRNA expression following 6 h of PGN challenge. PGN also acutely induced hemichannel activity in HeLa cells transfected to express Cx43, but had no effect in Cx43-deficient HeLa OHIO cells. All ATP responses were blocked with Cx-specific channel blockers. We conclude that acute Cx43 hemichannel signalling plays a role in the initiation of early innate immune responses in the endothelium.
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Research Article|
October 25 2010
Peptidoglycan derived from Staphylococcus epidermidis induces Connexin43 hemichannel activity with consequences on the innate immune response in endothelial cells
Jennifer Robertson;
Jennifer Robertson
*Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, Scotland, U.K.
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Sue Lang;
Sue Lang
*Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, Scotland, U.K.
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Peter A. Lambert;
Peter A. Lambert
†School of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.
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Patricia E. Martin
Patricia E. Martin
1
*Department of Biological and Biomedical Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, Scotland, U.K.
1To whom correspondence should be addressed (email patricia.martin@gcu.ac.uk).
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Publisher: Portland Press Ltd
Received:
November 12 2009
Revision Received:
August 24 2010
Accepted:
September 03 2010
Accepted Manuscript online:
September 03 2010
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2010 Biochemical Society
2010
Biochem J (2010) 432 (1): 133–143.
Article history
Received:
November 12 2009
Revision Received:
August 24 2010
Accepted:
September 03 2010
Accepted Manuscript online:
September 03 2010
Citation
Jennifer Robertson, Sue Lang, Peter A. Lambert, Patricia E. Martin; Peptidoglycan derived from Staphylococcus epidermidis induces Connexin43 hemichannel activity with consequences on the innate immune response in endothelial cells. Biochem J 15 November 2010; 432 (1): 133–143. doi: https://doi.org/10.1042/BJ20091753
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