Vasopressin inhibits mitogen-activated protein kinases and activated protein-1 in macrophages.

ABSTRACT

OBJECTIVES: We have previously shown that vasopressin could inhibit the upregulation of inflammatory mediators. Expression of inflammatory mediators is tightly regulated by the upstream transcriptional pathway mitogen-activated protein kinases (MAPKs) and activated protein-1 (AP-1). In this study, we elucidated whether vasopressin could inhibit the upregulation of MAPKs/AP-1. METHODS: Murine macrophages (RAW264.7 cells) randomly received lipopolysaccharide (LPS; 100 ng/mL) or LPS plus vasopressin (1000 pg/mL) (designated as the LPS and the LPS+V groups, respectively). Control groups were run simultaneously. For MAPKs, cells were harvested at 0 minutes, 15 minutes, 30 minutes, 45 minutes, and 60 minutes after reaction. For AP-1, cells were harvested at 60 minutes after reaction. Between-group differences in MAPKs (i.e., extracellular regulated kinase, c-Jun N-terminal kinase, and p38 MAPK) and AP-1 expressions were compared. RESULTS: Immunoblotting assay data revealed that extracellular regulated kinase concentrations of the LPS+V group that harvested at 45 minutes and 60 minutes, but not at 15 minutes and 30 minutes, were significantly lower than those of the LPS group (p=0.005 and p=0.013). C-Jun N-terminal kinase concentrations of the LPS+V group that harvested at 15 minutes, 30 minutes, 45 minutes, and 60 minutes were also significantly lower than those of the LPS group (all p<0.001). Concentrations of p38 MAPK of the LPS+V group that harvested at 15 minutes, 30 minutes, and 45 minutes, but not at 60 minutes, were also significantly lower than those of the LPS group (all p<0.001). In addition, immunohistochemistry assay revealed that the AP-1 fluorescence signals of the LPS+V group were weaker than those of the LPS group. CONCLUSION: Vasopressin inhibits MAPKs and AP-1 in endotoxin-activated macrophages.