Anti-M₃ muscarinic cholinergic autoantibodies from patients with primary Sjögren's syndrome trigger production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E₂ (PGE₂) from the submandibular glands

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• 作者：Silvia Reina^a ; ^b ; Leonor Sterin-Borda^a ; ^b ; Daniela Passafaro^a ; Enri Borda^a ; ^b ; ^{enri@farmaco.odon.uba.ar}
• 关键词：Autoantibodies ; Anti-M₃ peptide IgG ; Sj&#xf6 ; gren's syndrome ; PGE₂ ; MMP-3
• 刊名：Archives of Oral Biology
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：56
• 期：5
• 页码：413-420
• 全文大小：413 K

文摘

Background

We demonstrated that serum immunoglobulin G (IgG) from patients with primary Sjögren's syndrome (pSS), interacting with the second extracellular loop of human glandular M₃ muscarinic acetylcholine receptors (M₃ mAChR), trigger the production of matrix metalloproteinase-3 (MMP-3) and prostaglandin E₂ (PGE₂).

Methods

Enzyme-linked immunosorbent assays (ELISAs) were performed in the presence of M₃ mAChR synthetic peptide as antigen to detect in serum the autoantibodies. Further, MMP-3 and PGE₂ production were determined in the presence of anti-M₃ mAChR autoantibodies.

Results

An association was observed between serum and anti-M₃ mAChR autoantibodies and serum levels of MMP-3 and PGE₂ in pSS patients. Thus, we established that serum anti-M₃ mAChR autoantibodies, MMP-3 and PGE₂ may be considered to be early markers of pSS associated with inflammation. Affinity-purified anti-M₃ mAChR peptide IgG from pSS patients, whilst stimulating salivary-gland M₃ mAChR, causes an increase in the level of MMP-3 and PGE₂ as a result of the activation of phospholipase A₂ (PLA₂) 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/PGE₂).