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TLR3-mediated apoptosis and activation of phosphorylated Akt in the salivary gland epithelial cells of primary Sjögren’s syndrome patients


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Title: TLR3-mediated apoptosis and activation of phosphorylated Akt in the salivary gland epithelial cells of primary Sjögren’s syndrome patients
Authors: Nakamura, Hideki / Horai, Yoshiro / Suzuki, Takahisa / Okada, Akitomo / Ichinose, Kunihiro / Yamasaki, Satoshi / Koji, Takehiko / Kawakami, Atsushi
Issue Date: Feb-2013
Publisher: Springer Verlag
Citation: Rheumatology International, 33(2), pp.441-450; 2013
Abstract: This study aimed at ascertain whether innate immunity is involved in the apoptosis of primary cultured salivary gland epithelial cells (SGECs) in primary Sjögren's syndrome (pSS). Induction of apoptosis of SGECs was performed using a TLR3 ligand, poly (I:C). Activation of phosphorylated-Akt (pAkt) and cleaved-caspase 3 was determined by Western blotting or immunofluorescence. Expression of TLR2 and TLR3 with pAkt was observed in cultured SGECs after 24-h stimulation with each ligand. Compared with stimulation with the peptidoglycan or lipopolysaccharide, that with poly (I:C) induced significant nuclear fragmentation, as determined by Hoechst staining (p = 0.0098). Apoptosis was confirmed by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining of SGECs from pSS patients and a normal subject. A significant increase in TUNEL-positive cells was observed by the addition of a PI3K inhibitor, LY294002. Poly (I:C) phosphorylated stress-activated protein kinase/Jun-terminal kinase and p44/42 MAP kinase as well as Akt. Furthermore, poly (I:C)-induced caspase 3 cleavage in SGECs was also inhibited by LY294002. Similar results were obtained using SGECs obtained from a normal subject. The results demonstrated for the first time that TLR3 induces the apoptotic cell death of SGECs via the PI3K-Akt signaling pathway.
Keywords: Akt / Caspase3 / MAP kinase / Sjögren's syndrome / TLR3
URI: http://hdl.handle.net/10069/31582
ISSN: 01728172
DOI: 10.1007/s00296-012-2381-9
Rights: © 2013 Springer-Verlag. / The original publication is available at springerlink.com
Type: Journal Article
Text Version: author
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/31582

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