Suppression of high-mobility group box 1 ameliorates xerostomia in a sjogren syndrome-triggered mouse model.

Xerostomia is a self-conscious symptom. High-mobility group box 1 (HMGB1) promotes pro-inflammatory effects in many diseases. This study aimed at clarifying the role of HMGB1 in sjogren syndrome (SS)-triggered xerostomia. The non-obese diabetic (NOD)/Ltj mice were used to establish a SS-triggered xerostomia model. The results showed that saliva production was decreased and anti-sjogren syndrome B (anti-SSB) level was increased in SS. PCR, western blot and immunohischemistry experiments indicated that the HMGB1 and aquaporin 5 (AQP5) levels were enhanced and diminished in SS than those in Control, respectively. While the mice were treated with anti-HMGB1, xerostomia was reversed due to the elevated saliva production and reduced anti-SSB level. In addition, it was found that the inhibition of HMGB1 restrained the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) axis activation. The TLR4 and p-IκB levels were alleviated, whilst the IκBα and NF-κB p65 levels were augmented. NF-κB p65 the binding activity was attenuated via electrophoretic mobility shift assay (EMSA) after anti-HMGB1 treatment. Moreover, the repression of HMGB1 facilitated the expression of AQP5. These findings demonstrate that suppression of HMGB1 ameliorates SS-triggered xerostomia via suppressing HMGB1/TLR4/NF-κB signaling pathway and upregulating AQP5 expression.