PMID- 21371688 OWN - NLM STAT- MEDLINE DCOM- 20110922 LR - 20151119 IS - 1879-1506 (Electronic) IS - 0003-9969 (Linking) VI - 56 IP - 5 DP - 2011 May TI - Anti-M(3) muscarinic cholinergic autoantibodies from patients with primary Sjogren's syndrome trigger production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)) from the submandibular glands. PG - 413-20 LID - 10.1016/j.archoralbio.2010.08.017 [doi] AB - BACKGROUND: We demonstrated that serum immunoglobulin G (IgG) from patients with primary Sjogren's syndrome (pSS), interacting with the second extracellular loop of human glandular M(3) muscarinic acetylcholine receptors (M(3) mAChR), trigger the production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E(2) (PGE(2)). METHODS: Enzyme-linked immunosorbent assays (ELISAs) were performed in the presence of M(3) mAChR synthetic peptide as antigen to detect in serum the autoantibodies. Further, MMP-3 and PGE(2) production were determined in the presence of anti-M(3) mAChR autoantibodies. RESULTS: An association was observed between serum and anti-M(3) mAChR autoantibodies and serum levels of MMP-3 and PGE(2) in pSS patients. Thus, we established that serum anti-M(3) mAChR autoantibodies, MMP-3 and PGE(2) may be considered to be early markers of pSS associated with inflammation. Affinity-purified anti-M(3) mAChR peptide IgG from pSS patients, whilst stimulating salivary-gland M(3) mAChR, causes an increase in the level of MMP-3 and PGE(2) as a result of the activation of phospholipase A(2) (PLA(2)) and cyclooxygenase-2 (COX-2) (but not COX-1). CONCLUSIONS: These results provide a novel insight into the role that cholinoceptor antibodies play in the development of glandular inflammation. This is the first report showing that an antibody interacting with glandular mAChR can induce the production of pro-inflammatory mediators (MMP-3/PGE(2)). CI - Copyright (c) 2010 Elsevier Ltd. All rights reserved. FAU - Reina, Silvia AU - Reina S AD - Pharmacology Unit, School of Dentistry, University of Buenos Aires, Argentina. FAU - Sterin-Borda, Leonor AU - Sterin-Borda L FAU - Passafaro, Daniela AU - Passafaro D FAU - Borda, Enri AU - Borda E LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110303 PL - England TA - Arch Oral Biol JT - Archives of oral biology JID - 0116711 RN - 0 (Autoantibodies) RN - 0 (Biomarkers) RN - 0 (Immunoglobulin G) RN - 0 (Receptors, Muscarinic) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (PTGS2 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) SB - IM MH - Adult MH - Analysis of Variance MH - Autoantibodies/*immunology MH - Biomarkers/metabolism MH - Chromatography, Affinity MH - Cyclooxygenase 2/*immunology/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Humans MH - Immunoglobulin G/*immunology MH - Matrix Metalloproteinase 3/*immunology/metabolism MH - Middle Aged MH - Receptors, Muscarinic/*immunology MH - Sjogren's Syndrome/*immunology/metabolism MH - Submandibular Gland/*immunology/metabolism EDAT- 2011/03/05 06:00 MHDA- 2011/09/23 06:00 CRDT- 2011/03/05 06:00 PHST- 2010/05/06 00:00 [received] PHST- 2010/08/12 00:00 [revised] PHST- 2010/08/24 00:00 [accepted] PHST- 2011/03/05 06:00 [entrez] PHST- 2011/03/05 06:00 [pubmed] PHST- 2011/09/23 06:00 [medline] AID - S0003-9969(10)00259-1 [pii] AID - 10.1016/j.archoralbio.2010.08.017 [doi] PST - ppublish SO - Arch Oral Biol. 2011 May;56(5):413-20. doi: 10.1016/j.archoralbio.2010.08.017. Epub 2011 Mar 3.