Table 2.

Mechanisms of IL-33 and its related-cytokines

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