Role of salivary caspase‑1 and gasdermin D in the pathophysiology of rheumatoid arthritis in relation to salivary pH and flow rate of saliva

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting extra‑articular organs, manifesting as symmetric polyarticular invasive joint inflammation. The disease pathogenesis involves cell death caused by lysis, known as pyroptosis, leading to the development of inflammation. Cytokines that promote inflammation, such as IL‑18 and IL‑1β, are released as a result of the NLRP3 inflammasome activating caspase (CASP)1, 3 and 4. Notably, the gasdermin D (GSDMD)‑N‑terminal allows substances to flow through the plasma membrane, and this protein is cleaved by CASP1 and other caspases. The present study aimed to evaluate the role of salivary CASP1 and GSDMD in the pathophysiology of RA, and determine the roles of the salivary flow rate and saliva pH. A control group and two groups of patients, including newly diagnosed and treated patients with RA, were enrolled in the present study. An independent rheumatologist rated the clinical disease activity score of each patient, and the saliva pH and salivary flow rate were also measured. In addition, ELISA was used to detect the expression levels of CASP1 and GSDMD. The results of the present study revealed that the CASP1 level was significantly increased in all patients with RA, compared with the control group. Notably, the levels of CASP1 differed between the treated patients with RA and those newly diagnosed with RA. The results also revealed that there were no significant differences in the levels of GSDMD between the groups. Moreover, there were significant differences in the mean saliva pH and salivary flow rate between all patients with RA and the control group. On the whole, the present study demonstrates that GSDMD and CASP1 may be required for the development of RA. Following the activation of CASP1, the development of RA is promoted via signals that amplify inflammatory responses. Understanding the specific roles of these signals may lead to the development of novel therapeutic approaches.