Περίληψη:
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. (C) 2010 Elsevier Ltd. All rights reserved.
Συγγραφείς:
Manoussakis, Menelaos N.
Spachidou, Maria P.
Maratheftis,
Christos I.
