Mitogen-activated protein (MAP) kinases play a critical role in innate immune responses to microbial infection through eliciting the biosynthesis of proinflammatory cytokines. MAP phosphatases (MKP)-1 is an archetypical member of the dual-specificity phosphatase family that deactivates MAP kinases. Induction of MKP-1 has been implicated in attenuating the lipopolysaccharide (LPS) and Peptidoglycan (PGN) responses, but how the expression of the MKP-1 is regulated is still not fully understood. Here, we show that inhibition of p38 MAP kinase by specific inhibitor SB 203580 or RNA interference (RNAi) markedly reduced the expression of MKP-1 in LPS or PGN-treated macrophages, which is correlated with prolonged activation of p38 and JNK. Depletion of MAPKAP kinase 2 (MK2), a downstream substrate of p38, by RNAi also inhibited the expression of MKP-1. The mRNA level of MKP-1 is not affected by inhibition of p38, but the expression of MKP-1 is inhibited by treatment of cycloheximide. Thus, p38 MAPK plays a critical role in mediating expression of MKP-1 at a post-transcriptional level. Furthermore, inhibition of p38 by SB 203580 prevented the expression of MKP-1 in LPS-tolerized macrophages, restored the activation of MAP kinases after LPS restimulation. These results indicate a critical role of p38-MK2-dependent induction of MKP-1 in innate immune responses.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2006.07.010DOI Listing

Publication Analysis

Top Keywords

expression mkp-1
24
map kinases
12
critical role
12
inhibition p38
12
mkp-1
11
innate immune
8
immune responses
8
induction mkp-1
8
expression
7
p38
7

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!