Interleukin 24: Difference between revisions
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consistent citation formatting; added a bit more details to the roles in cancer |
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Although it belongs to the same group of cytokines as [[IL-10 family|IL-10]], it has different effect on the immune system. IL-10 is suppressive cytokine and suppresses [[inflammation]] but IL-24 has immunomodulatory function. |
Although it belongs to the same group of cytokines as [[IL-10 family|IL-10]], it has different effect on the immune system. IL-10 is suppressive cytokine and suppresses [[inflammation]] but IL-24 has immunomodulatory function. |
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Beside the normal physiological roles, at supra-physiological levels, IL-24 inhibits tumor growth, invasion, [[metastasis]] and [[angiogenesis]].<ref name="pmid25001534">{{cite journal | vauthors = Menezes ME, Bhatia S, Bhoopathi P, Das SK, Emdad L, Dasgupta S, Dent P, Wang XY, Sarkar D, Fisher PB | title = MDA-7/IL-24: multifunctional cancer killing cytokine | journal = Advances in Experimental Medicine and Biology | volume = 818 | issue = | pages = 127–53 | date = 2014 | pmid = 25001534 | pmc = 4633013 | doi = 10.1007/978-1-4471-6458-6_6 }}</ref> |
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Beside the normal physiological role, IL-24 is also important in cancer.<ref>{{Citation|last=Menezes|first=Mitchell E.|title=MDA-7/IL-24: Multifunctional Cancer Killing Cytokine|date=2014|url=http://link.springer.com/10.1007/978-1-4471-6458-6_6|work=Anticancer Genes|volume=818|pages=127–153|editor-last=Grimm|editor-first=Stefan|publisher=Springer London|doi=10.1007/978-1-4471-6458-6_6|isbn=9781447164579|access-date=2019-09-24|last2=Bhatia|first2=Shilpa|last3=Bhoopathi|first3=Praveen|last4=Das|first4=Swadesh K.|last5=Emdad|first5=Luni|last6=Dasgupta|first6=Santanu|last7=Dent|first7=Paul|last8=Wang|first8=Xiang-Yang|last9=Sarkar|first9=Devanand}}</ref> |
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== Cancer == |
== Cancer == |
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Revision as of 16:07, 24 September 2019
Interleukin 24 (IL-24) is a protein that in humans is encoded by the IL24 gene.
IL-24 is a cytokine belonging to the IL-10 family of cytokines that signals through two heterodimeric receptors: IL-20R1/IL-20R2 and IL-22R1/IL-20R2. This interleukin is also known as melanoma differentiation-associated 7 (mda-7) due to its discovery as a tumour suppressing protein. IL-24 appears to control in cell survival and proliferation by inducing rapid activation of particular transcription factors called STAT1 and STAT3. This cytokine is predominantly released by activated monocytes, macrophages and T helper 2 (Th2) cells[5] and acts on non-haematopoietic tissues such as skin, lung and reproductive tissues. IL-24 performs important roles in wound healing, arthritis, psoriasis and cancer.[6][7][8] Several studies have shown that cell death occurs in cancer cells/cell lines following exposure to IL-24.[9][10] The gene for IL-24 is located on chromosome 1 in humans.[11]
Structure
IL-24 is a secreted protein that is highly conserved throughout evolution with sequence homology between species including yeast, dog, cat, monkey and cow. It is located on chromosome 1q32-33 in humans along with several other IL-10 cytokine family gene members. IL-24 encompasses seven exons and six introns. The cDNA of IL-24 is 1,718 base pairs in length and encodes a protein of 206 amino acid with a predicted molecular size of ˜24 kDa. IL-24 also contains an IL-10 signature motif at amino acids 101–121 shared by other IL-10 family member cytokines. IL-24 possibly can form functionally active dimers due to the presence of potential disulfide bonds. Researchers identified a number of splice variants of IL-24 lacking one or more exons.[12]
Function
IL-24 functions as a cytokine (at low concentrations). Its normal physiological role is connected with wound healing (In normal skin cells, it suppress keratinocyte proliferation during wound healing[13]), protection against diseases caused by bacteria (for example Mycobacterim tuberculosis, Salmonella typhimurium, Pseudomonas aeruginosa). It is also important in autoimmune diseases such as psoriasis, rheumatoid arthritis or spondyloarthropathy.
Although it belongs to the same group of cytokines as IL-10, it has different effect on the immune system. IL-10 is suppressive cytokine and suppresses inflammation but IL-24 has immunomodulatory function.
Beside the normal physiological roles, at supra-physiological levels, IL-24 inhibits tumor growth, invasion, metastasis and angiogenesis.[14]
Cancer
IL-24 is an immunomodulatory cytokine which can also display broad cancer-specific suppressor effects. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, sensitization to chemotherapy, and induction of cancer-specific apoptosis. Given its ubiquitous apoptotic effect on malignant cells, lack of an effect on normal cells, and absence of significant side effects, IL-24 is an important candidate for cancer therapy.[15]
IL-24 is able to induce apoptosis via both intracellular and extracellular signaling mechanisms. Secreted IL-24 protein induces a robust expression of endogenous IL-24 and subsequent induction of tumor-specific killing through an ER stress-mediated pathway as well as by ROS production. The ER stress is the initial pathway in IL-24-induced apoptosis.[15]
An important question, which remained unresolved, is why IL-24 has the abilities to selectively induce apoptosis in a large spectrum of human cancer-derived cell lines without harming normal cells. One possible reason for this differential killing effect involves inherent biochemical differences between normal and cancer cells (ER stress, ROS production and ceramide), another possibility is that IL-24 is able to target a molecule that only triggers apoptosis in cancer cells. The third option for this differential killing effect is that both of the above hypotheses are correct.[15]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000162892 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026420 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Poindexter NJ, Walch ET, Chada S, Grimm EA (September 2005). "Cytokine induction of interleukin-24 in human peripheral blood mononuclear cells". Journal of Leukocyte Biology. 78 (3): 745–52. doi:10.1189/jlb.0205116. PMID 16000394.
- ^ Wang M, Liang P (February 2005). "Interleukin-24 and its receptors". Immunology. 114 (2): 166–70. doi:10.1111/j.1365-2567.2005.02094.x. PMC 1782067. PMID 15667561.
- ^ Kragstrup TW, Otkjaer K, Holm C, Jørgensen A, Hokland M, Iversen L, Deleuran B (January 2008). "The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid arthritis and spondyloarthropathy" (PDF). Cytokine. 41 (1): 16–23. doi:10.1016/j.cyto.2007.10.004. PMID 18061474.
- ^ Kragstrup TW, Greisen SR, Nielsen MA, Rhodes C, Stengaard-Pedersen K, Hetland ML, et al. (March 2016). "The interleukin-20 receptor axis in early rheumatoid arthritis: novel links between disease-associated autoantibodies and radiographic progression". Arthritis Research & Therapy. 18 (1): 61. doi:10.1186/s13075-016-0964-7. PMC 4788924. PMID 26968800.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Fisher PB, Gopalkrishnan RV, Chada S, Ramesh R, Grimm EA, Rosenfeld MR, et al. (2003). "mda-7/IL-24, a novel cancer selective apoptosis inducing cytokine gene: from the laboratory into the clinic". Cancer Biology & Therapy. 2 (4 Suppl 1): S23-37. doi:10.4161/cbt.458. PMID 14508078.
- ^ Sauane M, Lebedeva IV, Su ZZ, Choo HT, Randolph A, Valerie K, et al. (May 2004). "Melanoma differentiation associated gene-7/interleukin-24 promotes tumor cell-specific apoptosis through both secretory and nonsecretory pathways". Cancer Research. 64 (9): 2988–93. doi:10.1158/0008-5472.CAN-04-0200. PMID 15126330.
- ^ IL24 GeneCard
- ^ Emdad L, Bhoopathi P, Talukdar S, Pradhan AK, Sarkar D, Wang XY, et al. (July 2019). "Recent insights into apoptosis and toxic autophagy: The roles of MDA-7/IL-24, a multidimensional anti-cancer therapeutic". Seminars in Cancer Biology. doi:10.1016/j.semcancer.2019.07.013. PMID 31356866.
- ^ Whitaker EL, Filippov VA, Duerksen-Hughes PJ (December 2012). "Interleukin 24: mechanisms and therapeutic potential of an anti-cancer gene". Cytokine & Growth Factor Reviews. 23 (6): 323–31. doi:10.1016/j.cytogfr.2012.08.004. PMID 22981288.
- ^ Menezes ME, Bhatia S, Bhoopathi P, Das SK, Emdad L, Dasgupta S, Dent P, Wang XY, Sarkar D, Fisher PB (2014). "MDA-7/IL-24: multifunctional cancer killing cytokine". Advances in Experimental Medicine and Biology. 818: 127–53. doi:10.1007/978-1-4471-6458-6_6. PMC 4633013. PMID 25001534.
- ^ a b c Persaud L, De Jesus D, Brannigan O, Richiez-Paredes M, Huaman J, Alvarado G, et al. (June 2016). "Mechanism of Action and Applications of Interleukin 24 in Immunotherapy". International Journal of Molecular Sciences. 17 (6): 869. doi:10.3390/ijms17060869. PMC 4926403. PMID 27271601.
{{cite journal}}: CS1 maint: unflagged free DOI (link)
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