Table 2 Mechanisms of IL-33 and its related-cytokines
From: Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation
Cytokines | Receptors | Pathways | Results |
|---|---|---|---|
IL-33 as a transcription factor | – | Interferes with the binding of p65 to κB consensus binding sites | Dampens the pro-inflammatory signaling pathway |
High level of IL-33 | ST2L | NF-κB signaling pathway Activates and recruits astrocytes Promotes microglia polarization to M1 Reinforces Th17 and Th1 cell functions | Induces the production of IL-6, IL-8, IL-17, IL-1β, TNF-α, IFN-γ, CCL2, GMF, NO, ROS Negative effect on synaptic plasticity |
Low level of IL-33 | ST2L | NF-κB, AP-1, and MAP kinases p38, JNK, and ERK1/2 signaling pathway Promotes microglia polarization to M2 Promotes Th cells polarization to Th2 and Treg Inhibits Th cells polarization into Th1 and Th17 Inhibits microglia polarization into M1 | Induces the production of IL-4, IL-5, IL-13, IL-10 Decreases the release of IL-17, IL-6, IL-12, IL-18, IFN-γ, IL-1β, TNF-α, CCL2, ROS, and NO Inhibits ERS, autophagy, and apoptosis Exerts a protective effect on synaptic plasticity |
IL-33 | sST2 | Compete with ST2 for IL-33 | Inhibits the effect of the IL-33/ST2L signaling pathway |
IL-4, IL-5, IL-13 | – | Inhibit NO production through STAT6 Increase BDNF in hippocampal astrocytes | Inhibit neuroinflammation Promote learning-dependent synapse formation |
TNF-α, IL-1β, IL-18, and IL-6, ROS, NO | – | NF-κB signaling pathway A-calcium–calmodulin-dependent protein kinase II, MAPK, and ERK pathways | Induce neuroinflammation Induce ERS, autophagy, and apoptosis Impair the synaptic plasticity |