Fig. 1
From: Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation
IL-33 intracellular pathways. (1) IL-33 is mainly produced by endothelial cells, astrocytes, and oligodendrocytes. Its receptor complex ST2L/IL-1RAcP is constitutively expressed by microglia, astrocytes, and neurons in the hippocampus, which is associated with cognitive function. (2) IL-33 binds to the cell surface receptor complex ST2L/IL-1RAcP and induces MyD88 recruitment to the complex. (3) sST2 as an inducible receptor competes with ST2L to bind IL-33 and inhibits IL-33/ST2L signaling pathway-related effects. (4) Receptor-associated MyD88 facilitates the activation of IRAK1 and IRAK4 with TRAF6 recruitment. IRAKs induce the activation of IκB-α and IKK resulting in NF-κB activation. (5) Activated MyD88 also induces the phosphorylation of kinases ERK, and p38, along with IRAKs-induced JNK resulting in AP-1 activation. (6) NF-κB and AP-1 induce the production of the Th2-associated cytokines, including IL-4, IL-5, and IL-13