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Interferon-alpha but not -beta genes require de novo protein synthesis for efficient expression in human monocytes.
Scand J Immunol 1992; 35(2):177-85SJ

Abstract

Monocytes produce interferon-alpha (IFN)-alpha) and -beta when human peripheral blood mononuclear cells (PBMCs) are stimulated in vitro by Sendai virus (SV). We found that about 70% of the IFN-producing cells (IPCs) expressed both IFN-alpha and -beta mRNA; the rest expressed only IFN-beta mRNA. In the presence of the protein synthesis inhibitor cycloheximide (CHX), the frequency of IFN-alpha mRNA-containing cells, measured after 6h, was decreased by 85-90%. Results of nuclear run-on transcription assays showed that CHX inhibited IFN-alpha gene expression. The frequency of IFN-beta mRNA-containing cells was not reduced by CHX. Actually, a threefold increase was observed at the lower CHX concentrations. Studies on the kinetics of IFN-alpha/beta mRNA induction showed that CHX accelerated the appearance of IFN-beta mRNA-containing cells, increased IFN-beta mRNA levels, and delayed the normally occurring post-inductional decrease of IFN-beta mRNA. Unexpectedly, an initially normal or even accelerated IFN-alpha mRNA response was seen in the presence of CHX during the first 3-4 h after SV stimulation. This occurred in a small proportion of the potential IPCs. However, CHX prevented the subsequent marked increase of IFN-alpha mRNA levels. Preincubation of PBMCs for 6 h in conditioned medium (CM) containing IFN and other cytokines prevented the CHX-mediated inhibition of IFN-alpha mRNA. Without preincubation this was not seen. The preincubation in CM caused an accelerated appearance of IFN-alpha mRNA, resembling that of IFN-beta mRNA. The results suggest that IFN-alpha and -beta genes are differentially regulated in the same monocytes, the former requiring de novo synthesis of intracellular protein(s) for efficient expression.

Authors+Show Affiliations

Interferon Laboratory, Uppsala University, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1310814

Citation

Gobl, A E., et al. "Interferon-alpha but Not -beta Genes Require De Novo Protein Synthesis for Efficient Expression in Human Monocytes." Scandinavian Journal of Immunology, vol. 35, no. 2, 1992, pp. 177-85.
Gobl AE, Cederblad B, Sandberg K, et al. Interferon-alpha but not -beta genes require de novo protein synthesis for efficient expression in human monocytes. Scand J Immunol. 1992;35(2):177-85.
Gobl, A. E., Cederblad, B., Sandberg, K., & Alm, G. V. (1992). Interferon-alpha but not -beta genes require de novo protein synthesis for efficient expression in human monocytes. Scandinavian Journal of Immunology, 35(2), pp. 177-85.
Gobl AE, et al. Interferon-alpha but Not -beta Genes Require De Novo Protein Synthesis for Efficient Expression in Human Monocytes. Scand J Immunol. 1992;35(2):177-85. PubMed PMID: 1310814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interferon-alpha but not -beta genes require de novo protein synthesis for efficient expression in human monocytes. AU - Gobl,A E, AU - Cederblad,B, AU - Sandberg,K, AU - Alm,G V, PY - 1992/2/1/pubmed PY - 1992/2/1/medline PY - 1992/2/1/entrez SP - 177 EP - 85 JF - Scandinavian journal of immunology JO - Scand. J. Immunol. VL - 35 IS - 2 N2 - Monocytes produce interferon-alpha (IFN)-alpha) and -beta when human peripheral blood mononuclear cells (PBMCs) are stimulated in vitro by Sendai virus (SV). We found that about 70% of the IFN-producing cells (IPCs) expressed both IFN-alpha and -beta mRNA; the rest expressed only IFN-beta mRNA. In the presence of the protein synthesis inhibitor cycloheximide (CHX), the frequency of IFN-alpha mRNA-containing cells, measured after 6h, was decreased by 85-90%. Results of nuclear run-on transcription assays showed that CHX inhibited IFN-alpha gene expression. The frequency of IFN-beta mRNA-containing cells was not reduced by CHX. Actually, a threefold increase was observed at the lower CHX concentrations. Studies on the kinetics of IFN-alpha/beta mRNA induction showed that CHX accelerated the appearance of IFN-beta mRNA-containing cells, increased IFN-beta mRNA levels, and delayed the normally occurring post-inductional decrease of IFN-beta mRNA. Unexpectedly, an initially normal or even accelerated IFN-alpha mRNA response was seen in the presence of CHX during the first 3-4 h after SV stimulation. This occurred in a small proportion of the potential IPCs. However, CHX prevented the subsequent marked increase of IFN-alpha mRNA levels. Preincubation of PBMCs for 6 h in conditioned medium (CM) containing IFN and other cytokines prevented the CHX-mediated inhibition of IFN-alpha mRNA. Without preincubation this was not seen. The preincubation in CM caused an accelerated appearance of IFN-alpha mRNA, resembling that of IFN-beta mRNA. The results suggest that IFN-alpha and -beta genes are differentially regulated in the same monocytes, the former requiring de novo synthesis of intracellular protein(s) for efficient expression. SN - 0300-9475 UR - https://www.unboundmedicine.com/medline/citation/1310814/Interferon_alpha_but_not__beta_genes_require_de_novo_protein_synthesis_for_efficient_expression_in_human_monocytes_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0300-9475&date=1992&volume=35&issue=2&spage=177 DB - PRIME DP - Unbound Medicine ER -