Tripterygium glycosides and mesenchymal stem cells combination alleviated Sjögren's syndrome Features in mice and modulated the GRO-α/CXCR2 axis.

OBJECTIVE: To investigate the efficacy and potential mechanisms of tripterygium glycosides (TG) and human umbilical cord mesenchymal stem cells (hUC-MSCs) in the treatment of primary Sjögren's syndrome (PSS). METHODS: Experimental Sjögren's syndrome (ESS) mice were administered TG (20 or 40 mg/kg/d, via oral gavage) and/or hUC-MSCs (1 × 10^6 cells/mouse, via tail vein injection) for a duration of 21 consecutive days. The parameters analyzed included saliva volume, lymphocytic infiltration in submandibular glands (SGs), serum cytokines, immunoglobulins, and the expression of the growth-related oncogene-alpha (GRO-α)/CXC chemokine receptor 2 (CXCR2) axis, as well as aquaporins (AQP1, AQP5). RESULTS: Co-treatment with TG and hUC-MSCs resulted in a significant increase in saliva volume and a reduction in lymphocytic infiltration within the SGs. Additionally, this treatment decreased levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α) while enhancing the levels of anti-inflammatory cytokines (IL-10, IL-13) in serum, and modulated T helper (Th) 1 and Th2 cell populations. Furthermore, the combination therapy effectively suppressed elevated levels of immunoglobulins (immunoglobulin (Ig) M, IgG, IgA) in ESS mice. Mechanistically, the co-treatment inhibited the GRO-α/CXCR2 axis and upregulated the expression of AQP1 and AQP5 in SGs. CONCLUSION: The findings of this study suggest that co-treatment with TG and hUC-MSCs mitigates the symptoms of PSS by modulating inflammatory and immune responses and by inhibiting the GRO-α/CXCR2 axis.