| First Author | Hammer M | Year | 2005 |
| Journal | Eur J Immunol | Volume | 35 |
| Issue | 10 | Pages | 2991-3001 |
| PubMed ID | 16184516 | Mgi Jnum | J:113501 |
| Mgi Id | MGI:3686846 | Doi | 10.1002/eji.200526192 |
| Citation | Hammer M, et al. (2005) Control of dual-specificity phosphatase-1 expression in activated macrophages by IL-10. Eur J Immunol 35(10):2991-3001 |
| abstractText | 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-kappaB 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 inhibition of p38 MAPK via sustained expression of DUSP1. |
