IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA

TJ Mitchell, M Naughton, P Norsworthy, KA Davies, MJ Walport, Bernard J Morley

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Abstract

We investigated the mechanisms underlying the regulation of complement genes C3 and C4 by IFN-gamma. IFN-gamma (500 U/ml, 24 h incubation) increased steady state mRNA levels for both C3 and C4 in three different cell types (Hep G2, U937, and primary fibroblasts). The response to IFN-gamma in Hep G2 cells was time and dose dependent. At all doses of IFN-gamma and at all incubation times, the transcription rate for these two genes, determined by nuclear run-on assays, was reduced (0.3 +/- 0.1; unstimulated rate = 1.00). The t1/2 of mRNA for C3 and C4 in unstimulated cells was 1.8 +/- 0.3 and 2.2 +/- 0.2 h, respectively. After high-dose IFN-gamma stimulation, both C3 and C4 mRNA levels remained at 100% with respect to baseline at 5 h, but after 12 h, levels fell to 13 +/- 2% (C3) and 8 +/- 3% (C4) of baseline values, giving a half-life for these mRNA species of between 5 and 12 h. IFN-gamma stimulation increased C3 and C4 protein synthesis measured at 24 h. We suggest that it is the increase in mRNA stability that is the major effector mechanism by which IFN-gamma regulates C3 and C4 gene expression.
Original languageEnglish
Pages (from-to)4429-4434
Number of pages6
JournalThe Journal of Immunology
Volume156
Issue number11
Publication statusPublished - Jun 1996

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Complement C4
Complement C3
Up-Regulation
Messenger RNA
Hep G2 Cells
RNA Stability
Genes
Half-Life
Fibroblasts
Gene Expression
Proteins

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Mitchell, TJ., Naughton, M., Norsworthy, P., Davies, KA., Walport, MJ., & Morley, B. J. (1996). IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA. The Journal of Immunology, 156(11), 4429-4434.

IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA. / Mitchell, TJ; Naughton, M; Norsworthy, P; Davies, KA; Walport, MJ; Morley, Bernard J.

In: The Journal of Immunology, Vol. 156, No. 11, 06.1996, p. 4429-4434.

Research output: Contribution to journalArticle

Mitchell, TJ, Naughton, M, Norsworthy, P, Davies, KA, Walport, MJ & Morley, BJ 1996, 'IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA', The Journal of Immunology, vol. 156, no. 11, pp. 4429-4434.
Mitchell TJ, Naughton M, Norsworthy P, Davies KA, Walport MJ, Morley BJ. IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA. The Journal of Immunology. 1996 Jun;156(11):4429-4434.
Mitchell, TJ ; Naughton, M ; Norsworthy, P ; Davies, KA ; Walport, MJ ; Morley, Bernard J. / IFN-gamma up-regulates expression of the complement components C3 and C4 by stabilization of mRNA. In: The Journal of Immunology. 1996 ; Vol. 156, No. 11. pp. 4429-4434.
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AB - We investigated the mechanisms underlying the regulation of complement genes C3 and C4 by IFN-gamma. IFN-gamma (500 U/ml, 24 h incubation) increased steady state mRNA levels for both C3 and C4 in three different cell types (Hep G2, U937, and primary fibroblasts). The response to IFN-gamma in Hep G2 cells was time and dose dependent. At all doses of IFN-gamma and at all incubation times, the transcription rate for these two genes, determined by nuclear run-on assays, was reduced (0.3 +/- 0.1; unstimulated rate = 1.00). The t1/2 of mRNA for C3 and C4 in unstimulated cells was 1.8 +/- 0.3 and 2.2 +/- 0.2 h, respectively. After high-dose IFN-gamma stimulation, both C3 and C4 mRNA levels remained at 100% with respect to baseline at 5 h, but after 12 h, levels fell to 13 +/- 2% (C3) and 8 +/- 3% (C4) of baseline values, giving a half-life for these mRNA species of between 5 and 12 h. IFN-gamma stimulation increased C3 and C4 protein synthesis measured at 24 h. We suggest that it is the increase in mRNA stability that is the major effector mechanism by which IFN-gamma regulates C3 and C4 gene expression.

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