Paeoniflorin ameliorates symptoms of experimental Sjogren's syndrome associated with down-regulating Cyr61 expression

• Cyr61 expression is enhanced in the salivary glands of primary sjogren's syndrome patients and inflammatory salivary tissues of experimental sjogren's syndrome (ESS) mice.
• Blocking Cyr61 alleviates inflammation in submandibular gland of ESS.
• PF ameliorates symptoms of ESS associated with reducing expression of Cyr61.
• Targeting Cyr61 might be a potential means for the treatment of primary sjogren's syndrome.

Paeoniflorin (PF), an active compound extracted from Paeony root, has been used in therapy of autoimmune diseases with effective clinical efficiency and higher safety. Sjogren's syndrome (SS) is a chronic, systemic, immune-mediated inflammatory disease. In this study, we demonstrated that novel pro-inflammatory factor Cyr61/CCN1 was up-regulated in epithelial cells of salivary glands of primary SS patients and submandibular gland autoantigen-induced experimental SS mice. Blocking Cyr61 expression with special monoclonal antibody improved saliva secretion by ameliorating inflammatory infiltration and cytokines production in vivo. Furthermore, we showed that PF could alleviate inflammation by down-regulating Cyr61 expression in experimental SS mice. In conclusion, our new findings revealed for the first time that Cyr61 involves the pathogenesis of primary SS and PF alleviates SS-like symptoms associated with inhibiting Cyr61 expression, providing new insights into the potential molecular mechanism of PF in primary SS treatment.