Mechanism of Action and Applications of Interleukin 24 in Immunotherapy.
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.
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. leah.persaud@lehman.cuny.edu.|Department of Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, Room 4315, New York, NY 10016, USA. leah.persaud@lehman.cuny.edu.
Leah
L
Persaud
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. dayenny.dejesus@lc.cuny.edu.
Dayenny
D
De Jesus
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. brannigan.oliver@gmail.com.
Oliver
O
Brannigan
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. mariarichiez@gmail.com.
Maria
M
Richiez-Paredes
Department of Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, Room 4315, New York, NY 10016, USA. jhuaman08@gmail.com.|Department of Biological Sciences, Hunter College, City University of New York, 695 Park Avenue (at 68th street) HN927, New York, NY 10065, USA. jhuaman08@gmail.com.
Jeannette
J
Huaman
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. galvarado7@gmail.com.
Giselle
G
Alvarado
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. lindarr@optonline.net.
Linda
L
Riker
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. gissete.mendez@lc.cuny.edu.
Gissete
G
Mendez
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. jordan.dejoie@lc.cuny.edu.
Jordan
J
Dejoie
Department of Biological Sciences, Herbert H. Lehman College, City University of New York, 250 Bedford Park Boulevard West, Bronx, NY 10468, USA. moira.sauane@lehman.cuny.edu.|Department of Biology, The Graduate Center, City University of New York, 365 Fifth Avenue, Room 4315, New York, NY 10016, USA. moira.sauane@lehman.cuny.edu.
Moira
M
Sauane
D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D060467:Disease Resistance / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D007107:Immune System / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D007378:Interleukins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000235:genetics; D011485:Protein Binding; D018123:Receptors, Interleukin / Q000378:metabolism; D015398:Signal Transduction; D014945:Wound Healing / Q000235:genetics / Q000276:immunology; D000099180:Interleukin-24
D007378:Interleukins; D018123:Receptors, Interleukin; D000099180:Interleukin-24; C492510:interleukin-20 receptor
IL-24; Sigma 1 Receptor; cancer; endoplasmic reticulum (ER) stress; inflammatory disease