Gonadotropin-Releasing Hormone Modulates Immune System Function via the Nuclear Factor-kappa B Pathway in Murine Raw264.7 Macrophages

Abstract

Gonadotropin-releasing hormone (GnRH), which was originally found to be involved in the reproductive process, has also been implicated in the modulation of immune system function. However, the underlying mechanisms of this involvement remain largely unclear. In this study, we found that GnRH increased the intracellular calcium levels in murine Raw264.7 macrophages. Furthermore, the production of nitric oxide, costimulated with lipopolysaccharide and interferon-gamma, was suppressed by exposure to GnRH. Moreover, the modulatory effects of GnRH on calcium and nitric oxide were observed in freshly isolated primary peritoneal macrophages. In addition, the activity of nuclear factor-kappa B was suppressed by GnRH exposure. On the other hand, the phosphorylation of the Janus kinase-signal transducer and activator of transcription pathway was not affected by cotreatment with GnRH. Taken together, these results demonstrate that GnRH participates in the macrophage function and indicate that the nuclear factor-kappa B signaling pathway may be responsible for GnRH-mediated immune system modulation. Copyright (C) 2009 S. Karger AG, Basel