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Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein.

Publication ,  Journal Article
Haraguchi, S; Good, RA; Cianciolo, GJ; James-Yarish, M; Day, NK
Published in: J Immunol
September 1, 1993

We have previously shown that a synthetic peptide (CKS-17) homologous to retroviral envelope protein suppresses the accumulation of superantigen staphylococcal enterotoxin-induced TNF-alpha mRNA in human PBMC and in highly purified human monocytes. The present study was designed to examine the underlying mechanism(s) by which CKS-17 down-regulates the TNF-alpha mRNA expression using a human acute monocytic leukemia cell line THP-1 stimulated with the superantigen staphylococcal enterotoxin E. A cyclooxygenase inhibitor indomethacin does not reverse the inhibition of TNF-alpha mRNA expression by CKS-17, suggesting that prostaglandins are not responsible for the suppressive action of CKS-17. The inhibitory effect of CKS-17 is, however, significantly blocked by a protein synthesis inhibitor cycloheximide, indicating that CKS-17 requires de novo protein synthesis to induce the suppressive activity. The mRNA stability assays using actinomycin D show that CKS-17 does not decrease the TNF-alpha mRNA stability. Nuclear run-on transcription assays further reveal that CKS-17 suppresses the TNF-alpha mRNA transcription rate. Taken together, these results suggest that the synthetic retroviral peptide CKS-17 down-regulates TNF-alpha mRNA expression through inhibition of transcriptional activation of the TNF-alpha gene, which requires de novo synthesis of a transcriptional repressor protein(s).

Duke Scholars

Published In

J Immunol

ISSN

0022-1767

Publication Date

September 1, 1993

Volume

151

Issue

5

Start / End Page

2733 / 2741

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Retroviridae Proteins, Oncogenic
  • Peptides
  • Molecular Sequence Data
  • Interleukin-1
  • Intercellular Signaling Peptides and Proteins
  • Indomethacin
 

Citation

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Haraguchi, S., Good, R. A., Cianciolo, G. J., James-Yarish, M., & Day, N. K. (1993). Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein. J Immunol, 151(5), 2733–2741.
Haraguchi, S., R. A. Good, G. J. Cianciolo, M. James-Yarish, and N. K. Day. “Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein.J Immunol 151, no. 5 (September 1, 1993): 2733–41.
Haraguchi S, Good RA, Cianciolo GJ, James-Yarish M, Day NK. Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein. J Immunol. 1993 Sep 1;151(5):2733–41.
Haraguchi S, Good RA, Cianciolo GJ, James-Yarish M, Day NK. Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein. J Immunol. 1993 Sep 1;151(5):2733–2741.

Published In

J Immunol

ISSN

0022-1767

Publication Date

September 1, 1993

Volume

151

Issue

5

Start / End Page

2733 / 2741

Location

United States

Related Subject Headings

  • Viral Envelope Proteins
  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Transcription, Genetic
  • Retroviridae Proteins, Oncogenic
  • Peptides
  • Molecular Sequence Data
  • Interleukin-1
  • Intercellular Signaling Peptides and Proteins
  • Indomethacin