Human chorionic gonadotropin suppresses activation of nuclear transcription factor-kappa B and activator protein-1 induced by tumor necrosis factor

Human chorionic gonadotropin (hCG) suppresses cell-mediated allogeneic reac tions, viral replication, tumorigenesis, and metastasis, most of which requ ire activation of nuclear transcription factor-kappa B (NF-kappa B) and act ivator protein-1 (AP-1), In the present report, we investigated the effect of hCG on NF-kappa B and AP-1 activated by tumor necrosis factor (TNF). Tre atment of the CaCOV3 human ovarian cell line with hCG blocked TNF-induced a ctivation of NF-kappa B, I kappa B alpha degradation, and NF-kappa B-depend ent reporter gene transcription, hCG also blocked NF-kappa B activation ind uced by ceramide. The effect of hCG on NF-kappa B was mediated through inhi bition of phosphorylation of I kappa B alpha. Because hCG also blocked TNF receptor-associated factor-2 and NF-kappa B-inducing kinase reporter gene e xpression, hCG must act at a step that causes phosphorylation of I kappa B alpha, AP-1 activation induced by TNF and ceramide was also suppressed by h CG. hCG abrogated the TNF-induced activation of mitogen-activated protein k inase kinase and c-Jun N-terminal kinase required for NF-kappa B and AP-1, respectively. Dideoxyadenosine and H-8 reversed the effect, and dibutyryl c AMP mimicked the effect, suggesting that hCG suppresses the transcription f actors through cAMP-induced protein kinase A pathway. Overall, our results indicate that hCG inhibits the activation of NF-kappa B and AP-1, which may be the molecular basis by which hCG suppresses viral replication, cell pro liferation, tumorigenesis, and metastasis.