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. |