The identification of C/EBPbeta as a transcription factor necessary for the induction of MAPK phosphatase-1 by toll-like receptor-4 ligand.
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.
Cho
Il Je
IJ
Innovative Drug Research Center for Metabolic and Inflammatory Disease, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Woo
Na Ri
NR
Kim
Sang Geon
SG