Interleukin-4 regulates macrophage interleukin-12 protein synthesis through a c-fos mediated mechanism

Sabita Roy, Richard Charboneau, Dean Melnyk, Roderick A. Barke

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background. Interleukin-4 (IL-4) treatment after lipopolysaccharide (LPS) induction inhibits macrophage (Mφ) IL-12 synthesis; however, IL-4 pretreatment (PreTx) primes the Mφ for increased LPS-induced IL-12 production. In this study we study the role of c-fos in the IL-4 priming of Mφ IL-12 synthesis. Methods. With a murine in vitro peritoneal Mφ model, we studied the effect of either c-fos deficiency (wild type, WT; homozygous c-fos knockout, Homo KO) or c-fos overexpression to study the role of c-fos in IL-4 priming of LPS-induced Mφ IL-12 synthesis. Results. (1) We first show that IL-4 PreTx results in a 72% decrease in Mφ c-fos mRNA compared with vehicle PreTx. (2) With respect to IL-12 p70 protein, IL-4 PreTx in the WT group increased LPS-induced Mφ IL-12 p70 2.2-fold compared with vehicle PreTx. Compared with vehicle PreTx in the WT group, vehicle PreTx in the Homo KO group followed by LPS stimulation resulted in a 2.8-fold increase in IL-12 p70 in the Homo KO group. IL-4 PreTx did not significantly increase IL-12 p70 over vehicle PreTx in the Homo KO group. (3) We studied the effect of c-fos overexpression on LPS-induced Mφ IL-12 production when primed with IL-4. Overexpression of c-fos completely inhibited IL-4 primed LPS-induced IL-12 p70 protein synthesis. Conclusions. These data demonstrated that down-regulation of c-fos is an integral part of the IL-4 priming process for Mφ IL-12 production.

Original languageEnglish (US)
Pages (from-to)219-224
Number of pages6
JournalSurgery
Volume128
Issue number2
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

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Interleukin-12
Interleukin-4
Macrophages
Lipopolysaccharides
Proteins
Hominidae
Down-Regulation
Messenger RNA

ASJC Scopus subject areas

  • Surgery

Cite this

Interleukin-4 regulates macrophage interleukin-12 protein synthesis through a c-fos mediated mechanism. / Roy, Sabita; Charboneau, Richard; Melnyk, Dean; Barke, Roderick A.

In: Surgery, Vol. 128, No. 2, 01.01.2000, p. 219-224.

Research output: Contribution to journalArticle

Roy, Sabita ; Charboneau, Richard ; Melnyk, Dean ; Barke, Roderick A. / Interleukin-4 regulates macrophage interleukin-12 protein synthesis through a c-fos mediated mechanism. In: Surgery. 2000 ; Vol. 128, No. 2. pp. 219-224.
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abstract = "Background. Interleukin-4 (IL-4) treatment after lipopolysaccharide (LPS) induction inhibits macrophage (Mφ) IL-12 synthesis; however, IL-4 pretreatment (PreTx) primes the Mφ for increased LPS-induced IL-12 production. In this study we study the role of c-fos in the IL-4 priming of Mφ IL-12 synthesis. Methods. With a murine in vitro peritoneal Mφ model, we studied the effect of either c-fos deficiency (wild type, WT; homozygous c-fos knockout, Homo KO) or c-fos overexpression to study the role of c-fos in IL-4 priming of LPS-induced Mφ IL-12 synthesis. Results. (1) We first show that IL-4 PreTx results in a 72{\%} decrease in Mφ c-fos mRNA compared with vehicle PreTx. (2) With respect to IL-12 p70 protein, IL-4 PreTx in the WT group increased LPS-induced Mφ IL-12 p70 2.2-fold compared with vehicle PreTx. Compared with vehicle PreTx in the WT group, vehicle PreTx in the Homo KO group followed by LPS stimulation resulted in a 2.8-fold increase in IL-12 p70 in the Homo KO group. IL-4 PreTx did not significantly increase IL-12 p70 over vehicle PreTx in the Homo KO group. (3) We studied the effect of c-fos overexpression on LPS-induced Mφ IL-12 production when primed with IL-4. Overexpression of c-fos completely inhibited IL-4 primed LPS-induced IL-12 p70 protein synthesis. Conclusions. These data demonstrated that down-regulation of c-fos is an integral part of the IL-4 priming process for Mφ IL-12 production.",
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AB - Background. Interleukin-4 (IL-4) treatment after lipopolysaccharide (LPS) induction inhibits macrophage (Mφ) IL-12 synthesis; however, IL-4 pretreatment (PreTx) primes the Mφ for increased LPS-induced IL-12 production. In this study we study the role of c-fos in the IL-4 priming of Mφ IL-12 synthesis. Methods. With a murine in vitro peritoneal Mφ model, we studied the effect of either c-fos deficiency (wild type, WT; homozygous c-fos knockout, Homo KO) or c-fos overexpression to study the role of c-fos in IL-4 priming of LPS-induced Mφ IL-12 synthesis. Results. (1) We first show that IL-4 PreTx results in a 72% decrease in Mφ c-fos mRNA compared with vehicle PreTx. (2) With respect to IL-12 p70 protein, IL-4 PreTx in the WT group increased LPS-induced Mφ IL-12 p70 2.2-fold compared with vehicle PreTx. Compared with vehicle PreTx in the WT group, vehicle PreTx in the Homo KO group followed by LPS stimulation resulted in a 2.8-fold increase in IL-12 p70 in the Homo KO group. IL-4 PreTx did not significantly increase IL-12 p70 over vehicle PreTx in the Homo KO group. (3) We studied the effect of c-fos overexpression on LPS-induced Mφ IL-12 production when primed with IL-4. Overexpression of c-fos completely inhibited IL-4 primed LPS-induced IL-12 p70 protein synthesis. Conclusions. These data demonstrated that down-regulation of c-fos is an integral part of the IL-4 priming process for Mφ IL-12 production.

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