Switching Off Key Signaling Survival Molecules to Switch On the Resolution of Inflammation
Figure 1
Targets to promote granulocyte apoptosis and inflammation resolution. During early phase of inflammation production of proinflammatory mediators and activation of signal survival pathways (PI3K/Akt, NF-κB, MAPKs, and CDKs) promotes leukocyte accumulation and survival in the inflammatory site. While inflammatory response evolves, local activation/release of proresolution mediators occurs and pathways (H2O2, AnxA1, and cAMP) that control further granulocyte ingress and turn on a resolution program. These resolution molecules, in addition to proresolving lipid mediators which are not highlighted in this cartoon, downregulate survival pathways and activate an apoptosis-associated program in granulocytes. Resolution molecules are also able to promote efferocytosis and coordinate reprogramming of macrophages. These events will reestablish tissue homeostasis.
