| Project/Area Number |
24590773
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Hokkaido Institute of Public Health |
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Principal Investigator |
KOJIMA HIROYUKI 北海道立衛生研究所, 食品科学部, 主幹 (10414286)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEUCHI Shinji 北海道立衛生研究所, 理化学部, 主査 (20414287)
MUROMOTO Ryuta 北海道大学, 大学院薬学研究院, 助教 (30455597)
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| Co-Investigator(Renkei-kenkyūsha) |
MATSUDA Tadashi 北海道大学, 大学院薬学研究院, 教授 (20212219)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 環境化学物質 / AhR / IL17 / Th17 / ROR / 自己免疫疾患 / ダイオキシン / レポーターアッセイ |
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| Outline of Final Research Achievements |
The retinoic acid receptor-related orphan receptor (ROR) and aryl hydrocarbon receptor (AhR) are key regulators of helper T (Th)17 cell differentiation. However, it remains unclear whether environmental chemicals, including dioxins, affect Th17 cell functions. In this study, we examined the AhR activity of 200 environmental chemicals using DR-EcoScreen assay, and found that several pesticides and isoflavones enhanced AhR-mediated transcriptional activity. These compounds increased the expression of IL-17A mRNA without effecting ROR mRNA levels in mouse T lymphoma EL4 cells. On the other hand, these chemicals did not affect the IL-17A gene expression in ROR- or AhR-knockdown EL4 cells. Taken together, these results suggest that several AhR agonists might enhance IL-17 production via ROR and AhR. This study also provides the evidence that environmental chemicals can act as modulators of IL-17 gene expression in immune cells.
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