Cholinoreceptor autoantibodies in Sjögren syndrome.
Previous studies have demonstrated that antibodies against cholinoreceptors of exocrine glands correlate with dry mouth in persons with primary Sjögren syndrome (pSS). The aim of the present investigation was to establish if serum IgG antibodies (pSS IgG) were able to interact with cholinoreceptors in rat submandibular gland-dependent stimulation of cyclooxygenase 2 (COX-2) mRNA expression and PGE(2) production. Our findings indicated that pSS IgG-stimulating M(3), M(4), and M(1) cholinoreceptors exerted an increase in COX-2 mRNA without affecting COX-1 mRNA expression and increased PGE(2) production. Inhibitors of phospholipase A(2), COX- s, L-type calcium channel currents, and Ca(2+)-ATPase from sarcoplasmic reticulum prevented the pSS IgG effect on PGE(2) production. An ionophore of calcium mimicked pSS IgG action, suggesting a crucial role of calcium homeostasis in the cholinoreceptor-stimulated increase in PGE(2) production. Moreover, the amounts of PGE(2) in saliva and in sera from persons with pSS were significantly higher than in pre- or post-menopausal women. These findings illustrate the importance of autoantibodies to cholinoreceptors in the generation of chronic inflammation of target tissues in SS.
Reina
S
S
Pharmacology Unit, School of Dentistry, University of Buenos Aires, 1122 AAH, Buenos Aires, Argentina.
Orman
B
B
Anaya
J M
JM
Sterin-Borda
L
L
Borda
E
E
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000302:isolation & purification / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008875:Middle Aged; D018721:Muscarinic Agonists / Q000378:metabolism; D017698:Postmenopause; D051381:Rats; D011976:Receptors, Muscarinic / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*; D013363:Submandibular Gland / Q000276:immunology / Q000378:metabolism
D001323:Autoantibodies; D007074:Immunoglobulin G; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D002118:Calcium