Conditional expression of liver-enriched transcriptional activator protein augments Acholeplasma laidlawii-induced granulysin gene expression in a human monocytic cell line, THP-1

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Abstract
The antimicrobial protein granulysin is considered to play an important role in the defence mechanism against bacterial infection. We previously reported that Acholeplasma laidlawii-induced transactivation of the granulysin promoter in a human monocytic cell line, THP-1, is regulated by activator protein-1 and CCAAT/enhancer binding protein-beta (C/EBPbeta), but not by nuclear factor-kappaB. Moreover, liver-enriched transcriptional inhibitory protein (LIP), a C/EBPbeta isoform, was strongly induced in A. laidlawii-stimulated THP-1 cells. However, the level of liver-enriched transcriptional activator protein (LAP), another C/EBPbeta isoform, was essentially constant. Accordingly, we speculated that LIP would down-regulate A. laidlawii-induced granulysin gene expression in THP-1 cells. In the present study, we examined whether LAP augments A. laidlawii-induced granulysin gene expression using conditional LAP-expressing THP-1 cells in a tetracycline-controlled expression system. Our results indicated that conditional expression of LAP augmented A. laidlawii-induced expression of granulysin mRNA. In addition, the granulysin protein was observed in A. laidlawii-stimulated, LAP-expressing THP-1 cells. Our results suggest that the expression of LAP plays a critical role in the expression of the granulysin gene in macrophages.