PMID- 22513175
OWN - NLM
STAT- MEDLINE
DCOM- 20120629
LR  - 20120508
IS  - 1090-2163 (Electronic)
IS  - 0008-8749 (Linking)
VI  - 275
IP  - 1-2
DP  - 2012 Jan-Feb
TI  - Anti-M(3) peptide IgG from Sjogren's syndrome triggers apoptosis in A253 cells.
PG  - 33-41
LID - 10.1016/j.cellimm.2012.03.006 [doi]
AB  - Primary Sjogren's syndrome (pSS) is an autoimmune disease that targets salivary 
      and lachrymal glands, characterized by anti-cholinergic autoantibodies directed 
      against the M(3) muscarinic acetylcholine receptor (mAChR). The aim of this work 
      was to evaluate if cholinergic autoantibodies contained in IgG purified from 
      Sjogren sera could trigger apoptosis of A253 cell line. We also determined if 
      caspase-3 and matrix metalloproteinase-3 (MMP-3) are involved in the induction of 
      A253 cell death. Our results demonstrated that anti-cholinergic autoantibodies 
      stimulate apoptosis and inositol phosphate (InsP) accumulation accompanied by 
      caspase-3 activation and MMP-3 production. All of these effects were blunted by 
      atropine and J104794, indicating that M(3) mAChRs are impacted by the 
      anti-cholinergic autoantibodies. The intracellular pathway leading to 
      autoantibody-induced biological effects involves phospholipase C (PLC), 
      calcium/calmodulin (CaM) and extracellular calcium as demonstrated by treatment 
      with U-73122, W-7, verapamil, BAPTA and BAPTA-AM, all of which blocked the 
      effects of the anti-cholinergic autoantibodies. In conclusion, anti-cholinergic 
      autoantibodies in IgG purified from pSS patient's sera mediates apoptosis of the 
      A253 cell line in an InsP, caspase-3 and MMP-3 dependent manner.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Reina, Silvia
AU  - Reina S
AD  - Pharmacology Unit, School of Dentistry, Buenos Aires University and Argentine 
      National Research Council (CONICET), Ciudad Autonoma de Buenos Aires, Argentina. 
      slreina@yahoo.com
FAU - Sterin-Borda, Leonor
AU  - Sterin-Borda L
FAU - Borda, Enri
AU  - Borda E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120403
PL  - Netherlands
TA  - Cell Immunol
JT  - Cellular immunology
JID - 1246405
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptor, Muscarinic M3)
SB  - IM
MH  - Adult
MH  - *Apoptosis
MH  - Cell Line, Tumor
MH  - Female
MH  - Humans
MH  - Immunoglobulin G/*immunology/isolation & purification
MH  - Middle Aged
MH  - Peptide Fragments/immunology
MH  - Receptor, Muscarinic M3/*immunology
MH  - Sjogren's Syndrome/blood/*immunology/pathology
EDAT- 2012/04/20 06:00
MHDA- 2012/06/30 06:00
CRDT- 2012/04/20 06:00
PHST- 2011/10/13 00:00 [received]
PHST- 2012/03/06 00:00 [revised]
PHST- 2012/03/26 00:00 [accepted]
PHST- 2012/04/20 06:00 [entrez]
PHST- 2012/04/20 06:00 [pubmed]
PHST- 2012/06/30 06:00 [medline]
AID - S0008-8749(12)00056-1 [pii]
AID - 10.1016/j.cellimm.2012.03.006 [doi]
PST - ppublish
SO  - Cell Immunol. 2012 Jan-Feb;275(1-2):33-41. doi: 10.1016/j.cellimm.2012.03.006. 
      Epub 2012 Apr 3.