Modulation of c-Jun NH₂-Terminal (JNK) by Cholinergic Autoantibodies from Patients with Sjögren’s Syndrome  

作　　者：Enri Borda Daniela Passafaro Silvia Reina Leonor Sterin-Borda 

机构地区：[1]不详

出　　处：《Pharmacology & Pharmacy》2011年第4期256-265,共10页药理与制药（英文）

摘　　要：Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH2 terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (IgG) present in the sera of patients with primary Sj?gren’s syndrome (pSS) by interaction and activation of salivary gland muscarinic acetylcholine receptors (mAChRs). Methods: The JNK, PGE2 and NOS assays were measured in rat sub- mandibular gland with pSS IgG and carbachol alone or in the presence of different blocker agents. Results: pSS IgG- activated M3 mAChRs stimulated JNK phosphorylation whereas the activation of M1 mAChRs by carbachol stimulated JNK phosphorylation involving calcium-activated mechanism. The intracellular pathway leading to pSS IgG-induced biological effects on JNK activity involved activation of protein kinase C (PKC), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes. Also, activation of COX-2 and COX-1 by pSS IgG and carbachol-induced PGE2 generation were involved. Conclusion: These results may contribute to better understanding the modulatory role of JNK enzymes by cholinergic autoantibodies from pSS patients acting on mAChR in rat submandibular gland.Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH2 terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (IgG) present in the sera of patients with primary Sj?gren’s syndrome (pSS) by interaction and activation of salivary gland muscarinic acetylcholine receptors (mAChRs). Methods: The JNK, PGE2 and NOS assays were measured in rat sub- mandibular gland with pSS IgG and carbachol alone or in the presence of different blocker agents. Results: pSS IgG- activated M3 mAChRs stimulated JNK phosphorylation whereas the activation of M1 mAChRs by carbachol stimulated JNK phosphorylation involving calcium-activated mechanism. The intracellular pathway leading to pSS IgG-induced biological effects on JNK activity involved activation of protein kinase C (PKC), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes. Also, activation of COX-2 and COX-1 by pSS IgG and carbachol-induced PGE2 generation were involved. Conclusion: These results may contribute to better understanding the modulatory role of JNK enzymes by cholinergic autoantibodies from pSS patients acting on mAChR in rat submandibular gland.

关 键 词：JNK pSS IgG AUTOANTIBODIES PGE2 NOS CARBACHOL CHOLINERGIC Antagonists Enzymatic Inhibitors 

分 类 号：R73[医药卫生—肿瘤]