Zinc induces LPS-mediated upregulation of HBD-2 via ERK1/2 and p38MAPK signaling pathways in human prostate epithelial cells

초록

This study aimed to clarify the role of zinc in human prostate epithelial cell defense against bacterial infection. To explore the effect of zinc on lipopolysaccharide (LPS)-mediated induction of human beta-defensin-2 (HBD-2), the normal human prostate epithelial cell lines (RWPE-1) were co-treated with zinc/LPS and HBD-2 mRNA expression was quantitated by the reverse transcription polymerase chain reaction (RT-PCR). We also conducted a Western blot analysis to determine whether zinc stimulates p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase-1 and -2 (ERK1/2) signaling pathways. To investigate the involvement of the p38MAPK and ERK1/2 signaling pathways in zinc-mediated upregulation of HBD-2, quantitative real-time PCR and immunocytochemical staining were then used to quantify HBD-2 mRNA expression and protein production, respectively, which was treated with either U0126 (ERK1/2 inhibitor) or SB203580 (p38MAPK inhibitor) prior to each analysis of HBD-2. Cotreatment of RWPE-1 cells with zinc/LPS-upregulated HBD-2 expression to an even greater extent than either LPS alone or zinc alone. Moreover, the treatment of RWPE-1 cells with zinc significantly increased both the total and phosphorylated forms of ERK1/2 and p38MAPK. ERK1/2 and p38MAPK signaling via the inhibitors U0126 and SB203580 pharmacologically inhibited zinc-mediated upregulation of HBD2. These results strongly suggest that zinc plays an important role in the immune response of the prostate. Furthermore, we demonstrate that zinc-mediated upregulation of HBD-2 expression upon bacterial infection of prostate epithelial cells involves the ERK1/2 and p38MAPK signaling pathways.

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