[SIRT1 inhibits IL-1β mRNA transcription in lipopolysaccharide tolerant THP-1 cells]

Abstract

Objective: To explore the role of silent information regulation 2 homolog 1 (SIRT1) in the regulation of IL-1β mRNA transcription in lipopolysaccharide (LPS) tolerant THP-1 cells.

Methods: THP-1 human promonocyte model of endotoxin tolerance that simulates the sepsis leukocyte phenotype was used. Chromatin immunoprecipitation assay (ChIP) and real-time PCR were applied to quantify the binding of SIRT1 and histone H3 lys9/H4 lys16 acetylation to IL-1β promoter. IL-1β mRNA transcription was studied after knocking down the SIRT1.

Results: The binding of SIRT1 to IL-1β promoter increased about 5 times in tolerant THP-1 cells (P < 0.05), which was accompanied by the low level of histone H3 lys9/H4 lys16 acetylation (P < 0.05, compared with normal cells). Knocking-down of SIRT1 increased the transcription of IL-1β mRNA up to the level of 68% of normal cells (P < 0.05), which was accompanied by the increase of histone H3 lys9/H4 lys16 acetylation (P < 0.05). However, there was no significant difference of p65 lys310 acetylation between normal and tolerant cells.

Conclusion: SIRT1 inhibited the IL-1β mRNA transcription in tolerant THP-1 cells but had not related to p65 lys310 acetylation. However, it was related to IL-1β promoter acetylation.