Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Outline of Final Research Achievements |
Previously, we reported a positive feedback loop between S100A8/A9 and proinflammatory cytokines mediated by extracellular matrix metalloproteinase inducer (EMMPRIN), an S100A9 receptor. Therefore, we assumed that S100A8/A9 plays an important role in the chronic inflammation that arises from barrier disruption in atopic dermatitis. In this study, we identified neuroplastin-β (NPTNβ) as a novel S100A8 receptor. The S100A8-NPTNβ signal activated keratinocyte proliferation, while the S100A9-EMMPRIN signaling pathway induced skin inflammation. NPTNβ and EMMPRIN formed homodimers and a heterodimer. S100A8 and S100A9 were strongly expressed and co-localized with these receptors in the lesional skin of atopic dermatitis. These results indicate that NPTNβ and EMMPRIN form a functional heterodimeric receptor for S100A8/A9 and play a critical role in atopic dermatitis.
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