PMID- 25845745
OWN - NLM
STAT- MEDLINE
DCOM- 20150930
LR  - 20231213
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 181
IP  - 2
DP  - 2015 Aug
TI  - Endoplasmic reticulum stress causes autophagy and apoptosis leading to cellular 
      redistribution of the autoantigens Ro/Sjogren's syndrome-related antigen A (SSA) 
      and La/SSB in salivary gland epithelial cells.
PG  - 244-52
LID - 10.1111/cei.12638 [doi]
AB  - The aim of this study was to examine the levels of endoplasmic reticulum (ER) 
      stress in minor salivary glands, to investigate the interplay between ER 
      stress-induced autophagy and apoptosis in human salivary gland (HSG) cells and to 
      test the effect of ER stress-induced apoptosis on the cellular redistribution of 
      the two major Sjogren's syndrome (SS) autoantigens Ro/Sjogren's syndrome-related 
      antigen A (SSA) and La/Sjogren's syndrome-related antigen B (SSB). Minor salivary 
      gland biopsies from SS patients and sicca controls were examined by 
      immunohistochemistry for the expression of 78 kDa glucose-regulated 
      protein/binding immunoglobulin protein (GRP78/BiP) as an indicator of unfolded 
      protein response (UPR). HSG cells were treated with thapsigargin (TG) and cell 
      viability, autophagy and apoptosis were assessed. Immunoblot was applied to 
      detect the conversion of LC3I to LC3II and the protein levels of GRP78/BiP and 
      X-box binding protein-1 (XBP-1). Apoptosis was evaluated by a single-stranded DNA 
      enzyme-linked immunosorbent assay (ELISA). Ro/SSA and La/SSB localization was 
      visualized using immunofluorescence. GRP78/BiP was expressed by acinar and ductal 
      epithelial cells in salivary glands of patients and sicca controls. TG treatment 
      induced autophagy, as indicated by enhanced protein expression of LC3II. The 
      protein levels of UPR marker XBP-1 were increased after TG treatment, while 
      GRP78/BiP levels were decreased. TG treatment resulted in induction of HSG 
      apoptosis. Ro/SSA and La/SSB autoantigens were localized predominantly to the 
      cytoplasm in resting cells, while they were redistributed to cell membrane and 
      blebs in the apoptotic cells. In conclusion, ER stress is activated in minor 
      salivary gland epithelial cells from SS patients and controls. ER stress-induced 
      apoptosis in HSG cells leads to cell surface and apoptotic blebs relocalization 
      of Ro/SSA and La/SSB autoantigens.
CI  - (c) 2015 British Society for Immunology.
FAU - Katsiougiannis, S
AU  - Katsiougiannis S
AD  - Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
AD  - Dental Research Institute, UCLA School of Dentistry, Los Angeles, CA, USA.
FAU - Tenta, R
AU  - Tenta R
AD  - Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
FAU - Skopouli, F N
AU  - Skopouli FN
AD  - Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
AD  - Euroclinic of Athens, Department of Internal Medicine and Autoimmune Diseases, 
      Athens, Greece.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Autoantigens)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Endoplasmic Reticulum Chaperone BiP)
RN  - 0 (HSPA5 protein, human)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Ribonucleoproteins)
RN  - 0 (SS-A antigen)
RN  - 0 (Transcription Factors)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (XBP1 protein, human)
RN  - 67526-95-8 (Thapsigargin)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Autoantigens/*genetics/metabolism
MH  - Autophagy/drug effects
MH  - Cell Line
MH  - Cell Membrane/drug effects/metabolism/pathology
MH  - Cytoplasm/drug effects/metabolism/pathology
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Endoplasmic Reticulum Chaperone BiP
MH  - Endoplasmic Reticulum Stress/drug effects/*genetics
MH  - Epithelial Cells/drug effects/*metabolism/pathology
MH  - Female
MH  - Gene Expression Regulation
MH  - Heat-Shock Proteins/genetics/metabolism
MH  - Humans
MH  - Microtubule-Associated Proteins/genetics/metabolism
MH  - Primary Cell Culture
MH  - Protein Transport/drug effects
MH  - Regulatory Factor X Transcription Factors
MH  - Ribonucleoproteins/*genetics/metabolism
MH  - Salivary Glands, Minor/drug effects/*metabolism/pathology
MH  - Sjogren's Syndrome/*genetics/metabolism/pathology
MH  - Thapsigargin/pharmacology
MH  - Transcription Factors/genetics/metabolism
MH  - Unfolded Protein Response/drug effects
MH  - X-Box Binding Protein 1
MH  - SS-B Antigen
PMC - PMC4516440
OTO - NOTNLM
OT  - ER stress
OT  - La/SSB
OT  - Ro/SSA
OT  - Sjogren's syndrome
OT  - apoptosis
OT  - autoimmunity
OT  - autophagy
OT  - epithelial cells
EDAT- 2015/04/08 06:00
MHDA- 2015/10/01 06:00
PMCR- 2016/08/01
CRDT- 2015/04/08 06:00
PHST- 2014/12/11 00:00 [received]
PHST- 2015/03/30 00:00 [revised]
PHST- 2015/03/31 00:00 [accepted]
PHST- 2015/04/08 06:00 [entrez]
PHST- 2015/04/08 06:00 [pubmed]
PHST- 2015/10/01 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - 10.1111/cei.12638 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2015 Aug;181(2):244-52. doi: 10.1111/cei.12638.