S Roy1, R Charboneau, D Melnyk, R A Barke. 1. Departments of Surgery, Pharmacology, and Anesthesiology, University of Minnesota, Minneapolis Veterans Affairs Medical Center, 55417, USA.
Abstract
BACKGROUND: Interleukin-4 (IL-4) treatment after lipopolysaccharide (LPS) induction inhibits macrophage (Mphi) IL-12 synthesis; however, IL-4 pretreatment (PreTx) primes the Mphi for increased LPS-induced IL-12 production. In this study we study the role of c-fos in the IL-4 priming of Mphi IL-12 synthesis. METHODS: With a murine in vitro peritoneal M phi 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 M phi IL-12 synthesis. RESULTS: (1) We first show that IL-4 PreTx results in a 72% decrease in Mphi 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 Mphi 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 Mphi 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 Mphi IL-12 production.
BACKGROUND:Interleukin-4 (IL-4) treatment after lipopolysaccharide (LPS) induction inhibits macrophage (Mphi) IL-12 synthesis; however, IL-4 pretreatment (PreTx) primes the Mphi for increased LPS-induced IL-12 production. In this study we study the role of c-fos in the IL-4 priming of Mphi IL-12 synthesis. METHODS: With a murine in vitro peritoneal M phi 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 M phi IL-12 synthesis. RESULTS: (1) We first show that IL-4 PreTx results in a 72% decrease in Mphi 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 Mphi 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 Mphi 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 Mphi IL-12 production.
Authors: Jyoti V Thaikoottathil; Richard J Martin; Peter Y Di; Maisha Minor; Stephanie Case; Bicheng Zhang; Gongyi Zhang; Hua Huang; Hong Wei Chu Journal: Am J Respir Cell Mol Biol Date: 2012-04-12 Impact factor: 6.914
Authors: Adriana Pina; Rita C Valente-Ferreira; Eugênia E W Molinari-Madlum; Celidéia A C Vaz; Alexandre C Keller; Vera L G Calich Journal: Infect Immun Date: 2004-04 Impact factor: 3.441