Changes in Cyclooxygenase-2’s Expression, and PGE2 ’s and 6-keto-PGF1α’s Levels in the Presence of the Muscarinic Acethylcholine Receptor Antibody in Primary Sjögren Syndrome

Abstract

AbstractAims: This paper investigates the action of M3 muscarinic acetylcholine receptor antibody present in serum from patients with Sjögren syndrome (SS). Methods: Enzyme-linked immunoabsorbent assay (ELISA) was performed in the presence or absence of different enzymatic and specific receptors?antagonist drugs. The levels and the generation of PGE2, 6-keto-PGF1α and cyclic AMP (cAMP) in rat submandibular gland acini?s preparations and in serum from pSS patients were measured in the presence of pSS IgG anti M3 peptide. COX-2 mRNA gene?s expression at Real Time PCR was done in acini?s preparations from rat submandibular gland in the presence of the autoantibodies alone or once previously incubated with different inhibitors.Results: In this study, we show that the activation of M3 mAChR of rat submandibular gland acini?s preparation triggers an increment both in the production of COX-2 mRNA gene?s expression and in the production of PGE2 and 6-keto-PGF1α. These phenomena are accompanied by an increment in the production of cAMP in the acini?s preparation and do not affect COX-1 mRNA?s levels. Both prostanoids are augmented in the sera of pSS patients as compared with healthy individuals.Conclusions: The present study suggests a complex interplay between different factors involved in adaptativa autoimmunity in pSS patients at the level of exocrine glands. The presence of pSS IgG anti M3 peptide, the enhancement of COX-2 mRNA gene?s expression and the increment in the generation of PGE2 and 6-keto-PGF1α abolished by M3 specific cholinergic antagonist, could provide evidence of a link between autoimmunity and the submandibular gland parasympathetic system in the course of Sjögren?s syndrome. This evidence is further supported by an increment in the production of AMP cyclic nucleotide (cAMP), and the subsequent induction of desensitization, internalization and/or intracellular degradation of the glandular M3 mAChR displayed by the cholinergic autoantibody. All of these statements cited above, are responsible for xerostomy, xerophthalmia and other parasympathetic symptoms observed in SS patients.