Synonyms
Historical Background
Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines. Similar to IL-1β, IL-18 is synthesized as an inactive precursor requiring processing by caspase-1 into an active cytokine, but unlike IL-1β, the IL-18 precursor is constitutively present in all cells in healthy humans and animals. The activity of IL-18 is balanced by the presence of a high affinity, naturally occurring IL-18-binding protein (IL-18BP). IL-18 is synthesized as a biologically inactive precursor molecule lacking a signal peptide which requires cleavage into an active, mature molecule by the intracellular cysteine protease called IL-1beta-converting enzyme (ICE, also called caspase-1). The activity of mature IL-18 is closely related to that of IL-1. IL-18 induces gene expression and synthesis of tumor necrosis factor (TNF), IL-1, Fas ligand, and several chemokines. The activity of IL-18 is via an IL-18 receptor...
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References
Akamatsu S, Arai N, Hanaya T, Arai S, Tanimoto T, Fujii M, et al. Antitumor activity of interleukin-18 against the murine T-cell leukemia/lymphoma EL-4 in syngeneic mice. J Immunother. 2002;25(Suppl. 1):S28–34.
Alagkiozidis I, Facciabene A, Tsiatas M, et al. Time-dependent cytotoxic drugs selectively cooperate with IL-18 for cancer chemo-immunotherapy. J Transl Med. 2011;25:9–77.
Berasain C, Castillo J, Perugorria MJ, Latasa MU, Prieto J, Avila MA. Inflammation and liver cancer: new molecular links. Ann N Y Acad Sci. 2009;1155:206–21.
Chandrasekar B, Mummidi S, Mahimainathan L, Patel DN, Bailey SR, Imam SZ, Greene WC, Valente AJ. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. J Biol Chem. 2006;281:15099–109.
Cho D, Song H, Kim YM, Houh D, Hur DY, Park H, Yoon D, Pyun KH, Lee WJ, Kurimoto M, Kim YB, Kim YS, Choi I. Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of Fas ligand and reactive oxygen intermediates. Cancer Res. 2000;60(10):2703–9.
Clement M, Stamenkovic I. Superoxide anion is a natural inhibitor of Fas mediated cell death. EMBO J. 1996;15:216–25.
Coma G, Peña R, Blanco J, Rosell A, Borras FE, Esté JA, Clotet B, Ruiz L, Parkhouse RM, Bofill M. Treatment of monocytes with interleukin (IL)-12 plus IL-18 stimulates survival, differentiation and the production of CXC chemokine ligands (CXCL)8, CXCL9 and CXCL10. Clin Exp Immunol. 2006;145(3):535–44.
Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE, et al. Interleukin-12 and Interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest. 1998;101:1441–52.
Dobrovolskaia MA, Kozlov SV. Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership. Curr Cancer Drug Targets. 2005;5(5):325–44.
Han M-Y, Zheng S, Yu J-M, et al., Study on interleukin-18 gene transfer into human breast cancer cells to prevent tumorigenicity. J Zhejiang Univ Sci. 2004;5:472–6(5360).
Jiang D, Ying W, Lu Y, Wan J, Zhai Y, Liu W, Zhu Y, Qiu Z, Qian X, He F. Identification of metastasis associated proteins by proteomic analysis and functional exploration of interleukin-18 in metastasis. Proteomics. 2003;3(5):724–37.
Kim J, Shao Y, Kim SY, et al. Hypoxia-induced IL-18 increases hypoxia-inducible factor-1alpha expression through a Rac1-dependent NF-kappaB pathway. Mol Biol Cell. 2008;19:433–44.
Osaki T, Okamura H, Robbins PD, Kurimoto M, Nagata S, et al. Differential antitumoreffects of administration of recombinant IL-18 or recombinant IL-12 are mediated primarily by Fas–Fas ligand- and perforin-induced tumor apoptosis, respectively. J Immunol. 1999;163:583–9.
Park H, Byun D, Kim TS, Kim YI, Kang JS, Hahm ES, Kim SH, Lee WJ, Song HK, Yoon DY, Kang CJ, Lee C, Houh D, Kim H, Cho B, Kim Y, Yang YH, Min KH, Cho DH. Enhanced IL-18 expression in common skin tumors. Immunol Lett. 2001;79(3):215–9.
Quezada SA, Peggs KS, Curran MA, Allison JP. CTLA4 blockade and GM-CSF combination immunotherapy alters the intratumor balance of effector and regulatory T cells. J Clin Invest. 2006;116:1935–45.
Wang Q, Yu H, Ju DW, He L, Pan JP, Xia DJ, et al. Intratumoral IL-18 gene transfer improves therapeutic efficacy of antibody-targeted superantigen in established murine melanoma. Gene Ther. 2001;8:542–50.
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Palma, G. (2018). Interleukin-18. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101719
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101719
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