MKP-1 coordinates ordered macrophage-phenotype transitions essential for stem cell-dependent tissue repair

Resolution of inflammation: a new therapeutic frontier

“…By contrast, the exact role of p38 MAPK in the control of granulocyte survival is controversial; this pathway has been described to have both proapoptotic 85 and anti apoptotic 86 effects. During resolution, the restriction of p38 MAPK activation by MAPK phosphatase 1 controls the proinflammatory to antiinflammatory switch of macro phage polarization during muscle healing 87 . Further, during the non-phlogistic phagocytosis of apoptotic cells, the p38 MAPK signalling pathway leads to the activa tion of certain transcription factors that reprogramme the macro phage phenotype from proinflammatory to antiinflammatory, resulting in release of IL10 (REF.…”

Exercise and the Regulation of Inflammatory Responses

“…Namely, muscle recovery is largely dependent on the MAP kinase phosphatase-1 (MKP-1), which promotes p38 MAPK downregulation in macrophages, and subsequently promotes M1 to M2 macrophage differentiation. 26 Additionally, AMP-activated protein kinase (AMPK) alpha1 and cAMP response element-binding protein may also play integral roles in macrophage phenotype switching during muscle regeneration. 27 More recently, a unique population of T-regulatory cells has also been shown to be a key component to muscle repair and regeneration.…”

Cell death, clearance and immunity in the skeletal muscle

“…77,78 MAP kinase phosphatase-1 (MKP-1) regulates cell remnant disposal, macrophage transition and muscle healing. 79,80 Gene expression analyses on sorted MKP-1 − / − muscle macrophages suggest that MKP-1 regulates the inflammatory response as well as the macrophage polarization via p38 MAPK downregulation. Another enzyme, the AMP-activated protein kinase (AMPK)-α1, which 'senses' the cellular energy levels, also regulates the inflammatory status of macrophages.…”