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[NSD3 suppresses LPS-triggered TNF-α production via promoting the dimethylation of histone H3K36 in macrophages].

Objective To investigate the role of nuclear receptor-binding SET domain protein 3 (NSD3) in lipopolysaccharide (LPS)-triggered tumor necrosis factor α (TNF-α) production in macrophages and the underlying epigenetic mechanism. Methods The experiment used murine peritoneal macrophages and RAW264.7 cells as cell models. The mRNA and protein level of NSD3 were detected by real-time quantitative PCR and Western blot analysis in mouse peritoneal macrophages stimulated with LPS (100 ng/mL). ELISA was used to detect the production of TNF-α in NSD3-overexpressing RAW264.7 cells or NSD3-silencing peritoneal macrophages. Western blot analysis was performed to test the activation of LPS-triggered NF-κBp65 in NSD3-silencing macrophages. Luciferase assay was used to assess NF-κBp65-mediated transcriptional activation of TNF-α gene. ChIP assay was used to detect the recruitment of H3K36 methylation to TNF-α gene promoter. Results LPS inhibited the expression of NSD3 in the macrophages. Over-expression of NSD3 suppressed LPS-triggered TNF-α production, and silencing NSD3 promoted LPS-triggered TNF-α production. However, NSD3 had no effect on the activation of LPS-triggered NF-κBp65. NSD3 enhanced NF-κBp65-mediated transcriptional activation of TNF-α gene. NSD3 enhanced the dimethylation of H3K36 of TNF-α gene promoter. Conclusion NSD3 can promote the dimethylation of H3K36 of TNF-α gene promoter and suppress TNF-α transcription and production.