2001 Fiscal Year Final Research Report Summary
Role of Monocyte Chemoattractant Protein-1 (MCP-1) and regulation by NF-kB in Kawasaki disease
| Project/Area Number |
11670740
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | CHIBA UNIVERSITY |
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Principal Investigator |
TERAI Masaru Chiba University, Graduate School of Medicine, Lecturer, 大学院・医学研究院, 講師 (80207472)
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| Co-Investigator(Kenkyū-buntansha) |
JIBIKI Toshiaki Teikyo University, Ichihara Hospital, Assistant, 医学部・附属市原病院, 助手 (80235796)
OANA Shinji Chiba University, Graduate School of Medicine, Assistant, 大学院・医学研究院, 助手 (80292704)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Kawasaki disease / MCP-1 / Polymorphism |
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| Research Abstract |
Kawasaki disease (KD) is an acute febrile vasculitic syndrome of unknown etiology preferentially affecting Japanese children. In this project, we reported an enhanced expression of MCP-1 in the coronary vessels infiltrated by macrophages in fatal KD, suggesting a role of MCP-1 in the pathogenesis of KD.
Recently, the polymorphism at position -2518 (G or A), relative to the major transcriptional start site of the MCP-1 gene, was shown to influence the level of MCP-1 production in response to interleukin 1β in vitro (Rovin et al). We reproduced this in vitro effect of MCP-1 production using 18 Japanese healthy volunteers. PBMC from Japanese individuals who carry the -2518 G allele(high production of MCP-1) produced more MCP-1 than hoinozygotes for the A allele (low production of MCP-1) (p<0.01 by unpaired Welch's t test), consistent with an earlier study.
The A allele was found to be predominant among Caucasian and African American populations, suggesting a possible ethnic variation. The G/A polymorphism in Japanese population has not been investigated. Informed consent for this study was obtained from all subjects before the study. The observed genotype and allele frequencies showed that G allele (high production of MC-1 was largely predominant among the Japanese population. The frequency of the A allele was 35 % and that of the G allele was 65 %. In addition, the serum levels of MCP-1 in KD patients with G allele were higher than those in homozygotes for the A allele, although the statistical significance was not obtained when tested by Mann-Whitney U test (p = 0.24). In conclusion, the high prevalence of G allele in the distal regulatory region of the MCP-1 gene in Japanese may suggest a potentially important ethnic variation in the regulation of MCP-1 production, which may contribute to the pathogenesis of KD.
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[Publications] Terai, M., Yasukawa, K., Narumoto, S., Tateno, S., Oana, S., Kohno, Y.: "Vascular endothelial growth factor in acute Kawasaki disease."Am. J. Cardiol.. 83. 337-339.Am (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Terai. M., Jibiki. T., Harada, A., Teraishima, Y., Yasukawa, K., Tateno, S., Hamada, H., Oana, S., Niimi, H., Matsushima, K.: "Dramatic decrease of circulating levels of monocyte chemoattractant protein-1 in Kawasaki disease after gamma globulin treatment."J. Leukoc Biol.. 65. 566-572 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Rowley, A.H., Shulman.S.T., Mask, C.A., Finn., L., Terai. M., Mestecky, J., Baker, S.C., Galliani, C.A., Takahashi, K., Naoe, S., Kalelkar, M., Crawford, S.E.: "IgA plasma cell infiltration of upper respiratory tract, pancreas, kidney and coronary artery in acute Kawasaki disease."J. Infect. Dis.. 182(4). 1183-1191 (2000)
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[Publications] Tateno, S., Terai, M., Niwa, K., Jibiki, T., Hamada, H., Yasukawa, K., Honda, T., Oana, S., Kohno, Y.: "Alleviation of myocardial ischemia after Kawasaki disease by heparin and exercise therapy."Circulation. 103(21). 2591-2597 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Jibiki, T., Terai, M., Shima, M., Ogawa, A., Hamada, H. Kanazawa, M., Yamamoto, S., Oana, S., Kohno, Y.: "MCP-1 gene regulatory region polymorphism and serum MCP-1 levels in Japanese Kawasaki disease."Arthritis Rheum.. 44(9). 2211-2212 (2001)
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