Abstract
Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in cytokine-mediated activities. After exogenous addition of IL-24, apoptosis is induced in tumor cells independently of the JAK/STAT pathway. We have shown that IL-24 binds to Sigma 1 Receptor and this event induces endoplasmic reticulum stress, calcium mobilization, reactive oxygen species generation, p38MAPK activity, and ceramide production. Here we review IL-24’s role in autoimmunity, infectious disease response, wound repair, and vascular disease. Detailed understanding of the pleiotropic roles of IL-24 signaling can assist in the selection of more accurate therapeutic approaches, as well as targeting of appropriate cell types in treatment strategy development, and ultimately achieve desired therapeutic effects.
Highlights
Interleukin 24 (IL-24) belongs to the IL-10 cytokine family, which consists of nine related molecules: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29
These cytokines are classified into three subfamilies with different biological functions: The IL-10 subfamily represented by IL-10 itself; the IL-20 subfamily (IL-19, IL-20, IL-22, IL-24, and IL-26); and type III interferons (IFNs), IL-28A, IL-28B, and IL-29
We have demonstrated that IL-24 protein generates additional molecules of IL-24, inducing more endoplasmic reticulum (ER)-stress and culminating in an untenable imbalance resulting in apoptosis in cancer cells [22]
Summary
Interleukin 24 (IL-24) belongs to the IL-10 cytokine family, which consists of nine related molecules: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29. These cytokines are classified into three subfamilies with different biological functions: The IL-10 subfamily represented by IL-10 itself; the IL-20 subfamily (IL-19, IL-20, IL-22, IL-24, and IL-26); and type III interferons (IFNs), IL-28A, IL-28B, and IL-29. IL-24 is released by both immune and non-immune cells [1]. It is produced by peripheral blood mononuclear cells (PBMC), mostly monocytes, and T and B cells. To carry out several of its functions, IL-24 can signal through two types of membrane receptors (IL-22R1/IL-20R2 and IL-20R1/IL-20R2) with concurrent activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway within their cytoplasmic domains [3]
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