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*
Dipartimento di Medicina Sperimentale, Universita’ di Catanzaro, Catanzaro, Italy; and
Dipartimento di Medicina Interna, Universita’ di Roma Tor Vergata, Rome, Italy
An imbalance of immunoregulatory factors is believed to contribute
to uncontrolled mucosal Th1 cell activation in Crohn’s disease (CD).
IL-18, a macrophage-like cell-derived cytokine, is involved in Th1
clone development, and IFN-
production. Therefore, IL-18 expression
was investigated in CD. Whole mucosal intestinal tissue and lamina
propria mononuclear cells (LPMC) of 12 CD and 9 ulcerative colitis (UC)
patients and 15 non-inflammatory bowel disease (IBD) controls were
tested for IL-18 by semiquantitative RT-PCR and Western blot analysis.
Transcripts for IL-18 were found in all samples tested. However,
increased IL-18 mRNA accumulation was detected in both mucosal and LPMC
samples from CD in comparison to UC and controls. In CD, transcripts
for IL-18 were more abundant in the mucosal samples taken from involved
areas. An 18-kDa band consistent with mature IL-18 was predominantly
found in CD mucosal samples. In mucosal samples from non-IBD controls,
IL-18 was present as a 24-kDa polypeptide. Consistently, active
IL-1ß-converting enzyme (ICE) subunit (p20) was expressed in samples
from either CD or UC, whereas, in colonic mucosa from non-IBD controls,
ICE was synthesized as precursor (p45) only. To confirm that IL-18
produced in CD tissue was functionally active, CD LPMC were treated
with a specific IL-18 antisense oligonucleotide. In these cultures,
IL-18 down-regulation was accompanied by a decrease in IFN-
expression. In aggregate, our data indicate that IL-18 up-regulation is
a feature of CD and suggest that IL-18 may contribute to the local
immunoinflammatory response in CD.
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K. Shigehara, N. Shijubo, M. Ohmichi, R. Takahashi, S.-i. Kon, H. Okamura, M. Kurimoto, Y. Hiraga, T. Tatsuno, S. Abe, et al. IL-12 and IL-18 Are Increased and Stimulate IFN-{{gamma}} Production in Sarcoid Lungs J. Immunol., January 1, 2001; 166(1): 642 - 649. [Abstract] [Full Text] [PDF]
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T. Parrello, G. Monteleone, S. Cucchiara, I. Monteleone, L. Sebkova, P. Doldo, F. Luzza, and F. Pallone Up-Regulation of the IL-12 Receptor {beta}2 Chain in Crohn's Disease J. Immunol., December 15, 2000; 165(12): 7234 - 7239. [Abstract] [Full Text] [PDF]
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G. Cai, R. Kastelein, and C. A. Hunter Interleukin-18 (IL-18) Enhances Innate IL-12-Mediated Resistance to Toxoplasma gondii Infect. Immun., December 1, 2000; 68(12): 6932 - 6938. [Abstract] [Full Text] [PDF]
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S. Sugama, Y. Kim, H. Baker, C. Tinti, H. Kim, T. H. Joh, and B. Conti Tissue-Specific Expression of Rat IL-18 Gene and Response to Adrenocorticotropic Hormone Treatment J. Immunol., December 1, 2000; 165(11): 6287 - 6292. [Abstract] [Full Text] [PDF]
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L. A. B. Joosten, F. A. J. van de Loo, E. Lubberts, M. M. A. Helsen, M. G. Netea, J. W. M. van der Meer, C. A. Dinarello, and W. B. van den Berg An IFN-{gamma}-Independent Proinflammatory Role of IL-18 in Murine Streptococcal Cell Wall Arthritis J. Immunol., December 1, 2000; 165(11): 6553 - 6558. [Abstract] [Full Text] [PDF]
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F. Luzza, T. Parrello, G. Monteleone, L. Sebkova, M. Romano, R. Zarrilli, M. Imeneo, and F. Pallone Up-Regulation of IL-17 Is Associated with Bioactive IL-8 Expression in Helicobacter pylori-Infected Human Gastric Mucosa J. Immunol., November 1, 2000; 165(9): 5332 - 5337. [Abstract] [Full Text] [PDF]
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 C. K. Wong, E. K. Li, C. Y. Ho, and C. W. K. Lam Elevation of plasma interleukin-18 concentration is correlated with disease activity in systemic lupus erythematosus Rheumatology, October 1, 2000; 39(10): 1078 - 1081. [Abstract] [Full Text] [PDF]
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Y.-M. Kim, J. Y. Im, S. H. Han, H. S. Kang, and I. Choi IFN-{gamma} Up-Regulates IL-18 Gene Expression Via IFN Consensus Sequence-Binding Protein and Activator Protein-1 Elements in Macrophages J. Immunol., September 15, 2000; 165(6): 3198 - 3205. [Abstract] [Full Text] [PDF]
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A. Mencacci, A. Bacci, E. Cenci, C. Montagnoli, S. Fiorucci, A. Casagrande, R. A. Flavell, F. Bistoni, and L. Romani Interleukin 18 Restores Defective Th1 Immunity to Candida albicans in Caspase 1-Deficient Mice Infect. Immun., September 1, 2000; 68(9): 5126 - 5131. [Abstract] [Full Text] [PDF]
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B. P. Leung, I. B. McInnes, E. Esfandiari, X.-Q. Wei, and F. Y. Liew Combined Effects of IL-12 and IL-18 on the Induction of Collagen-Induced Arthritis J. Immunol., June 15, 2000; 164(12): 6495 - 6502. [Abstract] [Full Text] [PDF]
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 G. YAMADA, N. SHIJUBO, K. SHIGEHARA, H. OKAMURA, M. KURIMOTO, and S. ABE Increased Levels of Circulating Interleukin-18 in Patients with Advanced Tuberculosis Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1786 - 1789. [Abstract] [Full Text]
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K. Hoshino, S.-i. Kashiwamura, K. Kuribayashi, T. Kodama, T. Tsujimura, K. Nakanishi, T. Matsuyama, K. Takeda, and S. Akira The Absence of Interleukin 1 Receptor-Related T1/St2 Does Not Affect T Helper Cell Type 2 Development and Its Effector Function J. Exp. Med., November 15, 1999; 190(10): 1541 - 1548. [Abstract] [Full Text] [PDF]
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B. Siegmund, H.-A. Lehr, G. Fantuzzi, and C. A. Dinarello IL-1beta -converting enzyme (caspase-1) in intestinal inflammation PNAS, November 6, 2001; 98(23): 13249 - 13254. [Abstract] [Full Text] [PDF]
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