Dual-Specificity Phosphatase 1 and Tristetraprolin Cooperate To Regulate Macrophage Responses to Lipopolysaccharide.

摘要: Dual-specificity phosphatase (DUSP) 1 dephosphorylates and inactivates members of the MAPK superfamily, in particular, JNKs, p38α, p38β MAPKs. It functions as an essential negative regulator innate immune responses, hence disruption Dusp1 gene renders mice extremely sensitive to a wide variety experimental inflammatory challenges. The principal mechanisms behind overexpression mediators by Dusp1−/− cells are not known. In this study, we use genetic approach identify important mechanism action DUSP1, involving modulation activity mRNA-destabilizing protein tristetraprolin. This is key control early inflammation, TNF, CXCL1, CXCL2, well anti-inflammatory cytokine IL-10. same also contributes regulation large number transcripts induced treatment macrophages with LPS. These findings demonstrate that phosphorylation status tristetraprolin physiological which responses can be controlled.