PMID- 10788437
OWN - NLM
STAT- MEDLINE
DCOM- 20000601
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 18
DP  - 2000 May 5
TI  - Human chorionic gonadotropin suppresses activation of nuclear transcription 
      factor-kappa B and activator protein-1 induced by tumor necrosis factor.
PG  - 13307-14
AB  - Human chorionic gonadotropin (hCG) suppresses cell-mediated allogeneic reactions, 
      viral replication, tumorigenesis, and metastasis, most of which require 
      activation of nuclear transcription factor-kappaB (NF-kappaB) and activator 
      protein-1 (AP-1). In the present report, we investigated the effect of hCG on 
      NF-kappaB and AP-1 activated by tumor necrosis factor (TNF). Treatment of the 
      CaCOV3 human ovarian cell line with hCG blocked TNF-induced activation of 
      NF-kappaB, IkappaBalpha degradation, and NF-kappaB-dependent reporter gene 
      transcription. hCG also blocked NF-kappaB activation induced by ceramide. The 
      effect of hCG on NF-kappaB was mediated through inhibition of phosphorylation of 
      IkappaBalpha. Because hCG also blocked TNF receptor-associated factor-2 and 
      NF-kappaB-inducing kinase reporter gene expression, hCG must act at a step that 
      causes phosphorylation of IkappaBalpha. AP-1 activation induced by TNF and 
      ceramide was also suppressed by hCG. hCG abrogated the TNF-induced activation of 
      mitogen-activated protein kinase kinase and c-Jun N-terminal kinase required for 
      NF-kappaB and AP-1, respectively. Dideoxyadenosine and H-8 reversed the effect, 
      and dibutyryl cAMP mimicked the effect, suggesting that hCG suppresses the 
      transcription factors through cAMP-induced protein kinase A pathway. Overall, our 
      results indicate that hCG inhibits the activation of NF-kappaB and AP-1, which 
      may be the molecular basis by which hCG suppresses viral replication, cell 
      proliferation, tumorigenesis, and metastasis.
FAU - Manna, S K
AU  - Manna SK
AD  - Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of 
      Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
FAU - Mukhopadhyay, A
AU  - Mukhopadhyay A
FAU - Aggarwal, B B
AU  - Aggarwal BB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Cell Line
MH  - Chorionic Gonadotropin/*pharmacology
MH  - Drug Antagonism
MH  - Female
MH  - Humans
MH  - NF-kappa B/*metabolism
MH  - Signal Transduction/drug effects
MH  - Transcription Factor AP-1/*metabolism
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2000/05/02 09:00
MHDA- 2000/06/03 09:00
CRDT- 2000/05/02 09:00
PHST- 2000/05/02 09:00 [pubmed]
PHST- 2000/06/03 09:00 [medline]
PHST- 2000/05/02 09:00 [entrez]
AID - S0021-9258(19)80687-7 [pii]
AID - 10.1074/jbc.275.18.13307 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 May 5;275(18):13307-14. doi: 10.1074/jbc.275.18.13307.