Decreased SIRT1 protein may promote HMGB1 translocation in the keratinocytes of patients with cutaneous lupus erythematosus.

Background Ultraviolet radiation causes DNA damage in keratinocytes, aggravating cutaneous lupus erythematosus (CLE). High mobility group box 1 (HMGB1) participates in nucleotide excision and may transfer from the nucleus to the cytoplasm in immune active cells and the translocation of HMGB1 may result in DNA repair defects. HMGB1 was observed to transfer from the nucleus to the cytoplasm in the keratinocytes of CLE patients. As a class III histone deacetylases (HDACs), sirtuin-1 (SIRT1) can induce HMGB1 deacetylation. Epigenetic modification of HMGB1 may lead to HMGB1 translocation. Aims We aimed to evaluate the expressions of SIRT1 and HMGB1 in the epidermis of CLE patients and whether decreased SIRT1 leads to HMGB1 translocation through HMGB1 acetylation in keratinocytes. Methods We measured the messenger RNA (mRNA) and protein expressions of SIRT1 and HMGB1 in CLE patients using real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blotting. Keratinocytes were treated with SIRT1 activator resveratrol (Res) and irradiated with ultraviolet B (UVB). We detected the localization expression of HMGB1 by immunofluorescence. The apoptosis level and the cell cycle proportions were measured by flow cytometry. The acetyl-HMGB1 level was detected by immunoprecipitation. Results Compared to healthy controls, the mRNA and protein expressions of SIRT1 in the epidermis of CLE patients were significantly decreased and there was translocation of HMGB1 from the nucleus to the cytoplasm. In keratinocytes, UVB irradiation led to HMGB1 translocation from the nucleus to the cytoplasm. Res treatment inhibited HMGB1 translocation, attenuated the cell apoptosis induced by UVB and decreased the acetyl-HMGB1 level. Limitations We only treated keratinocytes with the SIRT1 activator but did not perform the relevant experiments in keratinocytes with SIRT1 knockdown or overexpression. In addition, the lysine residue site of action of SIRT1 deacetylation of HMGB1 is unclear. The specific mechanism of action of SIRT1 deacetylation of HMGB1 needs to be further investigated. Conclusion SIRT1 may inhibit HMGB1 translocation by HMGB1 deacetylation which inhibited the apoptosis of keratinocytes induced by UVB. Decreased SIRT1 may promote HMGB1 translocation in the keratinocytes of patients with CLE.