Change search
ReferencesLink to record
Permanent link

Direct link
Effects of the Escherichia coli toxin cytolysin A on mucosal immunostimulation via epithelial Ca2+ signalling and Toll-like receptor 4.
Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine). (Wai)
Show others and affiliations
2005 (English)In: Cell Microbiol, ISSN 1462-5814, Vol. 7, no 6, 779-88 p.Article in journal (Refereed) Published
Abstract [en]

Epithelial cells are vital to sense the presence of bacteria, thereby initiating a proper innate immune response. This occurs via different mechanisms, e.g. recognition by pattern recognition receptors (TLR), or alteration of the cellular Ca2+ homeostasis. The Escherichia coli toxin cytolysin A (ClyA) is naturally delivered to target cells as active pore assemblies within outer membrane vesicles (OMVs), and we here investigate a possible role of ClyA-containing OMVs (ClyA+ (OMV)) for induction of proinflammatory responses via the above-mentioned mechanisms. We report that low, sublytic concentrations of ClyA+ (OMV) affect the Ca2+ homeostasis in epithelial cells by induction of slow, intracellular Ca2+ oscillations, while increased concentrations act cytolytically. Thus, ClyA belongs to the novel group of pore-forming toxins shown to elicit such biphasic responses. Ca2+ waves in the minute range have been shown to regulate gene transcription of, e.g. interleukin (IL)-6 and -8. While the periodicity of ClyA+ (OMV)-induced Ca2+ waves (22.9 +/- 0.9 min) fail to induce an IL-8 response, our data fit to the general concept of frequency-specific gene expression. Molecular investigations of the signal transduction pathway reveals that ClyA+ (OMV) utilize a different one as compared with those previously reported for other toxins causing Ca2+ waves. The ClyA protein per se and ClyA pore assemblies are non-immunogenic, while lipopolysaccharide present on the OMVs induces a TLR4-dependent proinflammatory response as expected. Additional membrane components of the OMV, e.g. OmpW, was also found to elicit proinflammatory responses that was independent of TLR4 and Ca2+ signalling.

Place, publisher, year, edition, pages
2005. Vol. 7, no 6, 779-88 p.
Keyword [en]
Animals, Bacterial Outer Membrane Proteins/immunology, Calcium/metabolism, Calcium Signaling, Cells; Cultured, Epithelial Cells/*immunology/microbiology, Escherichia coli/immunology, Escherichia coli Proteins/immunology/*metabolism, Female, Hemolysin Proteins/*metabolism, Humans, Immunity; Mucosal, Immunity; Natural, Interleukin-6/metabolism, Interleukin-8/metabolism, Lipopolysaccharides/toxicity, Membrane Glycoproteins/*physiology, Rats, Rats; Sprague-Dawley, Receptors; Cell Surface/*physiology, Second Messenger Systems, Signal Transduction, Toll-Like Receptor 4, Toll-Like Receptors
URN: urn:nbn:se:umu:diva-16636PubMedID: 15888081OAI: diva2:156309
Available from: 2007-10-08 Created: 2007-10-08 Last updated: 2011-01-12Bibliographically approved

Open Access in DiVA

No full text

Other links


Search in DiVA

By author/editor
Wai, Sun NyuntUhlin, Bernt Eric
By organisation
Molecular Biology (Faculty of Medicine)

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 44 hits
ReferencesLink to record
Permanent link

Direct link