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,§,§
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Third Department of Internal Medicine,
Department of Immunology and Medical Zoology,
Department of Biochemistry and
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Laboratory of Host Defenses Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan;
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Fujisaki Institute, Hayashibara Biochemical Laboratories, Okayama, Japan;
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Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and
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Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
IL-18 is a powerful inducer of IFN-
production, particularly in
collaboration with IL-12. IL-18, like IL-12, also augments NK activity.
Here we investigated the molecular mechanism underlying the
up-regulation of killing activity of NK cells by IL-18. IL-18, like
IL-12, dose dependently enhanced NK activity of splenocytes. This
action was further enhanced by costimulation with IL-12. Treatment with
anti-IL-2R Ab did not affect IL-18- and/or IL-12-augmented NK
activity, and splenocytes from IFN--deficient mice showed enhanced
NK activity following stimulation with IL-12 and/or IL-18. Splenocytes
from the mice deficient in both IL-12 and IL-18 normally responded to
IL-18 and/or IL-12 with facilitated NK activity, suggesting that
functional NK cells develop in the absence of IL-12 and IL-18. IL-18R,
as well as IL-12R mRNA, was constitutively expressed in splenocytes
from SCID mice, which lack T cells and B cells but have intact NK
cells, and in those from IL-12 and IL-18 double knockout mice. NK cells
isolated from SCID splenocytes expressed IL-18R on their surface.
IL-18, in contrast to IL-12, did not enhance mRNA expression of
perforin, a key molecule for exocytosis-mediated cytotoxicity. However,
pretreatment with concanamycin A completely inhibited this IL-18-
and/or IL-12-augmented NK activity. Furthermore, IL-18, like IL-12,
failed to enhance NK activity of splenocytes from perforin-deficient
mice. These data suggested that NK cells develop and express IL-12R and
IL-18R in the absence of IL-12 or IL-18, and that both IL-18 and IL-12
directly and independently augment perforin-mediated cytotoxic activity
of NK cells.
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H. Kohka, M. Nishibori, H. Iwagaki, N. Nakaya, T. Yoshino, K. Kobashi, K. Saeki, N. Tanaka, and T. Akagi Histamine Is a Potent Inducer of IL-18 and IFN-{gamma} in Human Peripheral Blood Mononuclear Cells J. Immunol., June 15, 2000; 164(12): 6640 - 6646. [Abstract] [Full Text] [PDF]
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P. Hochholzer, G. B. Lipford, H. Wagner, K. Pfeffer, and K. Heeg Role of Interleukin-18 (IL-18) during Lethal Shock: Decreased Lipopolysaccharide Sensitivity but Normal Superantigen Reaction in IL-18-Deficient Mice Infect. Immun., June 1, 2000; 68(6): 3502 - 3508. [Abstract] [Full Text] [PDF]
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K. Ohkusu, T. Yoshimoto, K. Takeda, T. Ogura, S.-i. Kashiwamura, Y. Iwakura, S. Akira, H. Okamura, and K. Nakanishi Potentiality of Interleukin-18 as a Useful Reagent for Treatment and Prevention of Leishmania major Infection Infect. Immun., May 1, 2000; 68(5): 2449 - 2456. [Abstract] [Full Text] [PDF]
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C. L. Afonso, E. R. Tulman, Z. Lu, L. Zsak, G. F. Kutish, and D. L. Rock The Genome of Fowlpox Virus J. Virol., April 15, 2000; 74(8): 3815 - 3831. [Abstract] [Full Text]
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T. L. Born, L. A. Morrison, D. J. Esteban, T. VandenBos, L. G. Thebeau, N. Chen, M. K. Spriggs, J. E. Sims, and R. M. L. Buller A Poxvirus Protein That Binds to and Inactivates IL-18, and Inhibits NK Cell Response J. Immunol., March 15, 2000; 164(6): 3246 - 3254. [Abstract] [Full Text] [PDF]
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K. Tominaga, T. Yoshimoto, K. Torigoe, M. Kurimoto, K. Matsui, T. Hada, H. Okamura, and K. Nakanishi IL-12 synergizes with IL-18 or IL-1{beta} for IFN-{gamma} production from human T cells Int. Immunol., February 1, 2000; 12(2): 151 - 160. [Abstract] [Full Text] [PDF]
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E. Campbell, S. L. Kunkel, R. M. Strieter, and N. W. Lukacs Differential Roles of IL-18 in Allergic Airway Disease: Induction of Eotaxin by Resident Cell Populations Exacerbates Eosinophil Accumulation J. Immunol., January 15, 2000; 164(2): 1096 - 1102. [Abstract] [Full Text] [PDF]
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N. Hayashi, K. Matsui, H. Tsutsui, Y. Osada, R. T. Mohamed, H. Nakano, S.-i. Kashiwamura, Y. Hyodo, K. Takeda, S. Akira, et al. Kupffer Cells from Schistosoma mansoni-Infected Mice Participate in the Prompt Type 2 Differentiation of Hepatic T Cells in Response to Worm Antigens J. Immunol., December 15, 1999; 163(12): 6702 - 6711. [Abstract] [Full Text] [PDF]
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T. Kaisho, H. Tsutsui, T. Tanaka, T. Tsujimura, K. Takeda, T. Kawai, N. Yoshida, K. Nakanishi, and S. Akira Impairment of Natural Killer Cytotoxic Activity and Interferon {gamma} Production in CCAAT/Enhancer Binding Protein {gamma}-deficient Mice J. Exp. Med., December 6, 1999; 190(11): 1573 - 1582. [Abstract] [Full Text] [PDF]
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 T. Yoshimoto, H. Tsutsui, K. Tominaga, K. Hoshino, H. Okamura, S. Akira, W. E. Paul, and K. Nakanishi IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils PNAS, November 23, 1999; 96(24): 13962 - 13966. [Abstract] [Full Text] [PDF]
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N. Kayagaki, N. Yamaguchi, M. Nakayama, K. Takeda, H. Akiba, H. Tsutsui, H. Okamura, K. Nakanishi, K. Okumura, and H. Yagita Expression and Function of TNF-Related Apoptosis-Inducing Ligand on Murine Activated NK Cells J. Immunol., August 15, 1999; 163(4): 1906 - 1913. [Abstract] [Full Text] [PDF]
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R. Faggioni, J. Jones-Carson, D. A. Reed, C. A. Dinarello, K. R. Feingold, C. Grunfeld, and G. Fantuzzi Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: Role of tumor necrosis factor alpha and IL-18 PNAS, February 29, 2000; 97(5): 2367 - 2372. [Abstract] [Full Text] [PDF]
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