| Autor: |
Hammer, Michael, Mages, Jörg, Dietrich, Harald, Schmitz, Frank, Striebel, Frank, Murray, Peter J., Wagner, Hermann, Lang, Roland |
| Zdroj: |
European Journal of Immunology; Oct2005, Vol. 35 Issue 10, p2991-3001, 12p |
| Abstrakt: |
Ligation of Toll-like receptors (TLR) on macrophages induces cytokines and mediators important for the control of pathogens. Macrophage activation has to be tightly controlled to prevent hyper-inflammation. Accordingly, the hallmarks of TLR-triggered signaling, nuclear translocation of NF-κB and phosphorylation of mitogen-activated protein kinases (MAPK), are transient events. We have mined microarray datasets for changes in the expression of phosphatases in resting and TLR-activated macrophages. Several members of the dual-specificity phosphatases (DUSP) were induced upon triggering TLR4 with LPS. Up-regulation of DUSP1 mRNA was transient after stimulation with LPS alone, but addition of the immunosuppressive cytokine IL-10 resulted in robust, continued DUSP1 expression. IL-10 also synergized with the anti-inflammatory glucocorticoid dexamethasone in the induction of DUSP1 mRNA expression in activated macrophages, as well as in the inhibition of IL-6 and IL-12 production. Increased expression of DUSP1 in IL-10-treated activated macrophages was correlated with a faster down-regulation of p38 MAPK activation. Thus, these data suggest an operational link between IL-10 and inibition of p38 MAPK via sustained expression of DUSP1. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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