Cyclooxygenase 2 (COX-2) is an important inflammatory factor. Previous studies have indicated that COX-2 is induced with lipopolysaccharide (LPS) treatment. Here, we found that an inhibitor of histone deacetylase (HDAC), trichostatin A (TSA), cannot repress LPS-induced COX-2 but it increased the COX-2 level in RAW264.7 cells. We found no significant difference in NF-kappaB activation and ERK1/2 phosphorylation, but LPS-induced C/EBP delta expression was completely abolished after TSA treatment of LPS-treated cells. Interesting, reporter assay of C/EBP delta promoter revealed that Sp1-binding site is important. Although there was no alteration in c-Jun levels, but the phosphorylation of c-Jun at its C-terminus was increased dramatically. A DNA-associated protein assay (DAPA) and chromatin immunoprecipitation assay (ChIP) indicated that c-Jun was recruited via Sp1 to the promoter of C/EBP delta after LPS treatment; this recruitment of c-Jun was repressed by TSA. C/EBP delta inhibition by TSA resulted in increased binding of C/EBP alpha and C/EBP beta to the COX-2 promoter. Therefore, TSA has a positive effect on LPS-induced COX-2 since it decreases the C/EBP delta level by reducing c-Jun recruitment by Sp1 to the C/EBP delta promoter, resulting in increased the recruitment of C/EBP alpha and C/EBP beta to the COX-2 promoter.
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