| Salivary epithelial cells from Sjogren's syndrome patients are highly sensitive to anoikis induced by TLR-3 ligation. | |
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MedLine Citation:
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PMID: 20685081 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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In certain types of cells, Toll-like receptor-3 (TLR-3) ligation by viral dsRNA induces apoptotic death, likely engaged into the elimination of virus-infected cells. We have previously shown that TLR-3 ligation on cultured non-neoplastic salivary gland epithelial cells (SGEC) with polyI:C (a synthetic analogue of viral dsRNA) results in the induction of surface immunoactive molecules, however, the pro-apoptotic effect of such signaling has not been addressed. In this study, polyI:C-treated SGEC were found to suffer severe detachment from substratum and subsequent apoptosis, a phenomenon suggestive of anoikis or anoikia (detachment-induced apoptosis). PolyI:C-induced anoikis in SGEC was associated with the upregulation of the pro-apoptotic Bmf, BimEL and Bax and the down-regulation of the pro-survival Bcl-2 (real-time PCR analyses). Finally, the comparative analysis of SGEC lines derived from primary Sjogren's syndrome (SS) patients (SS-SGEC) and non-SS controls had revealed that SS-SGEC are particularly susceptible to TLR-3-induced anoikis, as it was triggered by suboptimally low concentrations of polyI:C. This finding correlated with significantly higher constitutive surface TLR-3 expression by SS-SGEC, a feature indicative of their intrinsic activation status. In conclusion, TLR-3 signaling pathway in the salivary epithelium appears to extend beyond the induction of innate immune responses and to involve the activation of programmed-cell death via anoikis. In the same context, the increased vulnerability of SS-SGEC to the injurious effect of TLR-3 ligation is likely associated with the intrinsic activation processes that apparently operate in the epithelia of SS patients, and a feature of key pathogenetic importance for the disorder. |
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Authors:
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Menelaos N Manoussakis; Maria P Spachidou; Christos I Maratheftis |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-03 |
Journal Detail:
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Title: Journal of autoimmunity Volume: 35 ISSN: 1095-9157 ISO Abbreviation: J. Autoimmun. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8812164 Medline TA: J Autoimmun Country: England |
Other Details:
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Languages: eng Pagination: 212-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Laboratory of Cellular and Molecular Immunology, Department of Pathophysiology, Medical School, National University of Athens, Greece. menman@med.uoa.gr |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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