Paeonol Reduces the Nucleocytoplasmic Transportation of HMGB1 by Upregulating HDAC3 in LPS-Induced RAW264.7 Cells

AbstractExtracellular high mobility group box 1 (HMGB1) is a lethal pro-inflammatory mediator in endotoxin shock. Hyperacetylation of HMGB1, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), changes its subcellular localization and secretion to the extracellular matrix. Paeonol (2 ′-hydroxy-4′-methoxyacetophenone), one of the main active components ofPaeonia suffruticosa, exerts anti-inflammatory effects. Our previous study demonstrated that Paeonol inhibited the relocation and secretion of HMGB1 in lipopolysaccharide (LPS)-activated RAW264.7 cells. However, it is still unclear whether Paeonol can regulate HATs/HDACs, which are responsible for the translocation of HMGB1 from nucleus to cytoplasm. To answer this question, P300 (a transcriptional coactivator with HATs) and HDAC3 were investigated using RT-qPCR and western blotting. The results showed that HMGB1 translocated from the nucleus to the cytoplasm, accompanied by upregulation of P300 and downregulation of HDAC3 in LPS-induced RAW264.7 cells. Paeonol, however, reversed the expression of P300 and HDAC3 significantly, suggesting that Paeonol may be involved in the acetylation of HMGB1 by regulating P300/HDAC3. Then, the effect of HDAC3 on the nucleocytoplasmic transportation of HMGB1 by HDAC3-SiRNA was evaluated. The results demonstrated that the inhibition of HDAC3 resulted in the nucleocytoplasmic translocation of HMGB1, with or without LPS stimulation. Moreover, Paeonol had no effect...
Source: Inflammation - Category: Allergy & Immunology Source Type: research