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

Abstract

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).

• Authors: S Haraguchi, R A Good, G J Cianciolo, M James-Yarish, N K Day
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 151 Issue 5 Pg. 2733-41 (Sep 01 1993) ISSN: 0022-1767 [Print] United States
• PMID: 8360488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enterotoxins
• Intercellular Signaling Peptides and Proteins
• Interleukin-1
• Peptides
• Retroviridae Proteins, Oncogenic
• Tumor Necrosis Factor-alpha
• Viral Envelope Proteins
• enterotoxin E, Staphylococcal
• Cycloheximide
• CKS 17
• Indomethacin

Topics

• Amino Acid Sequence
• Cycloheximide (pharmacology)
• Down-Regulation
• Enterotoxins (pharmacology)
• Gene Expression Regulation (drug effects)
• Humans
• Indomethacin (pharmacology)
• Intercellular Signaling Peptides and Proteins
• Interleukin-1 (genetics)
• Molecular Sequence Data
• Peptides (pharmacology)
• Retroviridae Proteins, Oncogenic (pharmacology)
• Transcription, Genetic (drug effects)
• Tumor Cells, Cultured
• Tumor Necrosis Factor-alpha (genetics)
• Viral Envelope Proteins (pharmacology)