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 language | English (US) |
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Pages (from-to) | 2596-2605 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 280 |
Issue number | 4 |
DOIs | |
State | Published - Jan 28 2005 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology