PMID- 9261427
OWN - NLM
STAT- MEDLINE
DCOM- 19970917
LR  - 20220228
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 71
IP  - 9
DP  - 1997 Sep
TI  - Induction of tumor necrosis factor alpha in human neuronal cells by extracellular 
      human T-cell lymphotropic virus type 1 Tax.
PG  - 6982-9
AB  - To examine the role of human T-lymphotropic virus type 1 (HTLV-1) Tax1 in the 
      development of neurological disease, we studied the effects of extracellular Tax1 
      on gene expression in NT2-N cells, postmitotic cells that share morphologic, 
      phenotypic, and functional features with mature human primary neurons. Treatment 
      with soluble HTLV-1 Tax1 resulted in the induction of tumor necrosis factor alpha 
      (TNF-alpha) gene expression, as detected by reverse-transcribed PCR and by 
      enzyme-linked immunosorbent assay. TNF-alpha induction was completely blocked by 
      clearance with anti-Tax1 monoclonal antibodies. Furthermore, cells treated with 
      either a mock bacterial extract or with lipopolysaccharide produced no detectable 
      TNF-alpha. Synthesis of TNF-alpha in response to soluble Tax1 occurred in a 
      dose-dependent fashion between 0.25 and 75 nM and peaked within 6 h of treatment. 
      Interestingly, culturing NT2-N cells in the presence of soluble Tax1 for as 
      little as 5 min was sufficient to result in TNF-alpha production, indicating that 
      the induction of TNF-alpha in NT2-N does not require Tax1 to be continually 
      present in the culture medium. Treatment of the undifferentiated parental 
      embryonal carcinoma cell line NT2 with soluble Tax1 did not result in TNF-alpha 
      synthesis, suggesting that differentiation-dependent, neuron-specific factors may 
      be required. These results provide the first experimental evidence that neuronal 
      cells are sensitive to HTLV-1 Tax1 as an extracellular cytokine, with a potential 
      role in the pathology of HTLV-1-associated/tropical spastic paraparesis.
FAU - Cowan, E P
AU  - Cowan EP
AD  - Division of Transfusion Transmitted Diseases, Food and Drug Administration, 
      Rockville, Maryland, USA. epc@helix.nih.gov
FAU - Alexander, R K
AU  - Alexander RK
FAU - Daniel, S
AU  - Daniel S
FAU - Kashanchi, F
AU  - Kashanchi F
FAU - Brady, J N
AU  - Brady JN
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Gene Products, tax)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Cell Differentiation
MH  - Cell Line
MH  - Gene Products, tax/*physiology
MH  - Human T-lymphotropic virus 1/*physiology
MH  - Humans
MH  - Kinetics
MH  - Mitosis
MH  - Neurons/cytology/*metabolism
MH  - Recombinant Fusion Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
PMC - PMC191983
EDAT- 1997/09/01 00:00
MHDA- 1997/09/01 00:01
PMCR- 1997/09/01
CRDT- 1997/09/01 00:00
PHST- 1997/09/01 00:00 [pubmed]
PHST- 1997/09/01 00:01 [medline]
PHST- 1997/09/01 00:00 [entrez]
PHST- 1997/09/01 00:00 [pmc-release]
AID - 10.1128/JVI.71.9.6982-6989.1997 [doi]
PST - ppublish
SO  - J Virol. 1997 Sep;71(9):6982-9. doi: 10.1128/JVI.71.9.6982-6989.1997.