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

S K Manna1, A Mukhopadhyay, B B Aggarwal

  • 1Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.

The Journal of Biological Chemistry
|May 2, 2000
PubMed

Insights

Human chorionic gonadotropin (hCG) inhibits key signaling pathways, nuclear transcription factor-kappaB (NF-kappaB) and activator protein-1 (AP-1). This suppression may explain how hCG reduces viral replication, cell proliferation, and metastasis.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Human chorionic gonadotropin (hCG) is known to modulate immune responses and inhibit processes like viral replication and cancer metastasis.
  • Many of these processes are regulated by the activation of nuclear transcription factor-kappaB (NF-kappaB) and activator protein-1 (AP-1).

Purpose of the Study:

  • To investigate the molecular mechanisms by which hCG affects the activation of NF-kappaB and AP-1.
  • To determine the specific signaling pathways involved in hCG's inhibitory effects.

Main Methods:

  • Utilized the CaCOV3 human ovarian cell line.
  • Stimulated cells with tumor necrosis factor (TNF) and ceramide to activate NF-kappaB and AP-1.
  • Assessed the impact of hCG on NF-kappaB and AP-1 activation using reporter gene assays and Western blotting to examine protein degradation and phosphorylation.
  • Investigated the role of the cAMP-dependent protein kinase A pathway.

Main Results:

  • hCG treatment blocked TNF- and ceramide-induced activation of NF-kappaB and AP-1.
  • hCG inhibited the phosphorylation of IkappaBalpha, a key step in NF-kappaB activation.
  • hCG suppressed the activation of upstream kinases, including mitogen-activated protein kinase kinase and c-Jun N-terminal kinase.
  • The effects of hCG were mimicked by dibutyryl cAMP and reversed by dideoxyadenosine and H-8, suggesting a role for the cAMP-induced protein kinase A pathway.

Conclusions:

  • hCG inhibits the activation of NF-kappaB and AP-1 through a mechanism involving the cAMP-induced protein kinase A pathway.
  • These findings provide a molecular basis for hCG's suppressive effects on viral replication, cell proliferation, tumorigenesis, and metastasis.

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