1. Adam D. Bachstetter 1 ;Linda J. Van Eldik 1, 2 ;
The p38 MAP Kinase Family as Regulators of Proinflammatory Cytokine Production in Degenerative Diseases of the CNS
Adam D. Bachstetter 1 ;Linda J. Van Eldik 1, 2 ;
1 Sanders-Brown Center on Aging ; 2 Dept Anatomy and Neurobiology, University of Kentucky Lexington, KY USA ;
Figure 2: Feedback mechanisms regulating p38 α. Inflammatory signals, such as TNFα and IL-1β, can activate the p38 pathway. Two downstream kinases of p38 are MK2 and MSK12. MK2 can promote an increase in TNFα, IL-1β and IL-6. These pro-inflammatory cytokines can then feed back onto the cell, activating the same pathway and amplifying the inflammation. MSK12 produces the phosphatase DUSP1, which dephosphorylates and deactivates p38. Two antiinflammatory cytokines IL-1ra and IL-10 are also regulated by MSK12 activation. These cytokines have the potential to antagonize the effects of IL-1β and suppress the inflammatory response.
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