Figure 1.

Schematic illustration showing the effect of IL-32. (A) Schematic illustration showing the effect of IL-32 on the BMP pathway and IL-6 induction. In the presence of BMP4, it feeds the loop and binds to the BMP receptor, activating SMAD and thus regulating gene expression. IL-6 is inhibited by this regulation. On the other hand, in the presence of IL-32, IL-6 is induced and activates several pathways. One of these pathways is ERK, which in turn inhibits SMAD. Therefore, IL-6 induced by IL-32 acts as negative feedback for the BMP pathway, as results of cell proliferation increased. IL-32 was found to increase the expression (either directly or indirectly) of the connective tissue growth factor (cTGF), as results of spindle-shape transformation increased, and thus invasion and metastasis occurred. (B) Schematic illustration showing the different effects of IL-32 isoform in AML. IL-32γ was shown to induce TNF-α production and activate NF-κB and MAPK signaling pathways and therefore, increased proliferation and survival. Whereas, IL-32θ was shown to inhibit TNF-α and phosphorylated p38 MAPK and NF-κB, thus, reducing cancer progression. This makes IL-32θ to be considered a potent inhibitor of TNF-α in patients with AML. Figure created by BioRender App.