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Publication : The identification of C/EBPbeta as a transcription factor necessary for the induction of MAPK phosphatase-1 by toll-like receptor-4 ligand.

First Author  Cho IJ Year  2008
Journal  Arch Biochem Biophys Volume  479
Issue  1 Pages  88-96
PubMed ID  18761321 Mgi Jnum  J:142443
Mgi Id  MGI:3821524 Doi  10.1016/j.abb.2008.08.007
Citation  Cho IJ, et al. (2008) The identification of C/EBPbeta as a transcription factor necessary for the induction of MAPK phosphatase-1 by toll-like receptor-4 ligand. Arch Biochem Biophys 479(1):88-96
abstractText  Toll-like receptor activates mitogen-activated protein kinases (MAPKs), which contributes to inflammatory responses. The activities of MAPKs are counter-balanced by MAPK phosphatases (MKPs). Because the transcriptional regulatory mechanism of mkp-1 has not been completely established, this study investigated the effect of toll-like receptor-4 ligand (TLR4L, lipopolysaccharide) on CCAAT/enhancer binding protein-beta (C/EBP beta)-dependent induction of MKP-1 in Raw264.7 cells. TLR4L treatment induced MKP-1 through gene transcription. Other TLRLs also transactivated mkp-1. Gel-shift, immunoblot and chromatin immunoprecipitation assays identified the activation of C/EBPbeta by TLR4L. Consistently, C/EBP beta transfection promoted mkp-1 transactivation, which was reversed by its dominant-negative mutant (AC/EBP). Experiments using chemical inhibitors or dominant-negative mutants of MAPKs indicated that both C/EBP beta activation and MKP-1 induction depend on the activation of MAPKs. TLR4L activation of C/EBP beta also contributed to the induction of dusp-2,dusp-4,dusp-8 and dusp-16. These results identify C/EBP beta as a transcription factor necessary for the induction of MKP-1 by TLRL.
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