Transcriptional down-regulation of tumor necrosis factor-alpha gene expression by a synthetic peptide homologous to retroviral envelope protein
| Autor: | S, Haraguchi, R A, Good, G J, Cianciolo, M, James-Yarish, N K, Day |
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| Rok vydání: | 1993 |
| Předmět: |
Transcription
Genetic Tumor Necrosis Factor-alpha Indomethacin Molecular Sequence Data Retroviridae Proteins Oncogenic Down-Regulation Enterotoxins Gene Expression Regulation Viral Envelope Proteins Tumor Cells Cultured Humans Intercellular Signaling Peptides and Proteins Amino Acid Sequence Cycloheximide Peptides Interleukin-1 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 151(5) |
| ISSN: | 0022-1767 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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