Early growth response-1 regulates lipopolysaccharide-induced suppressor of cytokine signaling-1 transcription

Justin Mostecki, Brian M. Showalter, Paul B Rothman

Research output: Contribution to journalArticle

Abstract

Suppressor of cytokine signaling (SOCS)-1 is a critical regulator of lipopolysaccharide (LPS) tolerance and LPS-induced cytokine production. The mechanisms regulating the transcription of SOCS-1 in response to LPS are not entirely understood. Functional analysis of the SOCS-1 promoter demonstrates that early growth response-1 (Egr-1) is an important transcriptional regulator of SOCS-1. Two Egr-1 binding sites are present within the SOCS-1 promoter as shown by EMSA and supershift analysis. Further, mutation of the Egr-1 binding sites significantly reduces both the basal and LPS-induced transcriptional activity of the promoter. Chromatin immunoprecipitation experiments confirm LPS-induced binding of Egr-1 to the SOCS-1 promoter in vivo. Additionally, Egr-1-/- macrophages show reduced levels of LPS-induced SOCS-1 expression in comparison with macrophages derived from Egr-1+/+ littermate controls. These results demonstrate an important role for Egr-1 in regulating both the basal and LPS-induced activity of the SOCS-1 promoter.

Original languageEnglish (US)
Pages (from-to)2596-2605
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number4
DOIs
StatePublished - Jan 28 2005
Externally publishedYes

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Transcription
Lipopolysaccharides
Cytokines
Growth
Macrophages
Binding Sites
Functional analysis
Chromatin Immunoprecipitation
Chromatin
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Early growth response-1 regulates lipopolysaccharide-induced suppressor of cytokine signaling-1 transcription. / Mostecki, Justin; Showalter, Brian M.; Rothman, Paul B.

In: Journal of Biological Chemistry, Vol. 280, No. 4, 28.01.2005, p. 2596-2605.

Research output: Contribution to journalArticle

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abstract = "Suppressor of cytokine signaling (SOCS)-1 is a critical regulator of lipopolysaccharide (LPS) tolerance and LPS-induced cytokine production. The mechanisms regulating the transcription of SOCS-1 in response to LPS are not entirely understood. Functional analysis of the SOCS-1 promoter demonstrates that early growth response-1 (Egr-1) is an important transcriptional regulator of SOCS-1. Two Egr-1 binding sites are present within the SOCS-1 promoter as shown by EMSA and supershift analysis. Further, mutation of the Egr-1 binding sites significantly reduces both the basal and LPS-induced transcriptional activity of the promoter. Chromatin immunoprecipitation experiments confirm LPS-induced binding of Egr-1 to the SOCS-1 promoter in vivo. Additionally, Egr-1-/- macrophages show reduced levels of LPS-induced SOCS-1 expression in comparison with macrophages derived from Egr-1+/+ littermate controls. These results demonstrate an important role for Egr-1 in regulating both the basal and LPS-induced activity of the SOCS-1 promoter.",
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N2 - Suppressor of cytokine signaling (SOCS)-1 is a critical regulator of lipopolysaccharide (LPS) tolerance and LPS-induced cytokine production. The mechanisms regulating the transcription of SOCS-1 in response to LPS are not entirely understood. Functional analysis of the SOCS-1 promoter demonstrates that early growth response-1 (Egr-1) is an important transcriptional regulator of SOCS-1. Two Egr-1 binding sites are present within the SOCS-1 promoter as shown by EMSA and supershift analysis. Further, mutation of the Egr-1 binding sites significantly reduces both the basal and LPS-induced transcriptional activity of the promoter. Chromatin immunoprecipitation experiments confirm LPS-induced binding of Egr-1 to the SOCS-1 promoter in vivo. Additionally, Egr-1-/- macrophages show reduced levels of LPS-induced SOCS-1 expression in comparison with macrophages derived from Egr-1+/+ littermate controls. These results demonstrate an important role for Egr-1 in regulating both the basal and LPS-induced activity of the SOCS-1 promoter.

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