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Epidermal growth factor inhibits Fas-mediated apoptosis in salivary epithelial cells of patients with primary Sjögren`s syndrome
H. Nakamura, A. Kawakami, H. Ida, T. Koji, K. Eguchi
CER3168
2007 Vol.25, N°6
PI 0831, PF 0837
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PMID: 18173916 [PubMed]
Abstract
OBJECTIVES:
Cell death is detected in the ducts of labial salivary glands (LSG) of patients with primary Sjögren`s syndrome (pSS). However, the counter-mechanism to inhibit the apoptotic process remains unclear. In this study, we studied the ability of epidermal growth factor (EGF) to activate the PI3K-Akt pathway and NF-kB in primary cultured salivary gland epithelial cells (SGEC) of pSS patients.
METHODS:
SGEC, obtained from 2 female pSS patients, were cultured and used for Hoechst staining and deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) assay. The frequency of apoptosis, detected by Hoechst staining, was quantified, and statistical significance was determined through unpaired student`s t-test.
RESULTS:
Following twelve hours of stimulation, both PI3K inhibitors and anti-Fas antibody failed to induce apoptosis in primary cultured SGEC. However, the combination of anti-Fas antibody, along with LY294002 or Bay 11-7082, induced apoptosis which was statistically more significant than apoptosis found in the control cells (p < 0.01). Interestingly, the apoptosis induced by anti-Fas antibody along with LY294002 was clearly inhibited by the addition of 10 ng/ml EGF. Furthermore, the results of the TUNEL assay clearly indicated apoptosis through stimulation with anti-Fas antibody and LY294002 or Bay 11-7082. Furthermore, the apoptosis was completely blocked by the addition of EGF.
CONCLUSIONS:
: Our results suggest that salivary epithelial cells are protected from Fas mediated apoptosis, through cell survival factors including either the PI3K-Akt pathway or NF-kB.


