Transcription profiling of spleens from dual specificity phosphatase-1 (DUSP1) deficient and wild type mice to demonstrate a specific regulatory role of DUSP1 on a subset of LPS-induced genes that control the outcome of endotoxin shock.

ABSTRACT: Activation of the Mitogen activated protein kinase (MAPK) cascade following Toll-like receptor (TLR) stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase Dual specificity phosphatase-1 (DUSP1) as an essential endogenous regulator of the inflammatory response to LPS. DUSP1-deficient (DUSP1-/-) bone marrow derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1-/- mice with LPS caused increased lethality and overshooting production of IL-6 and TNF. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induce

ORGANISM(S): Mus musculus

SUBMITTER: Roland Lang 

PROVIDER: E-GEOD-3565 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress