| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that recognizes a large number of xenobiotics, dioxins, and some endogenous ligands. Despite numerous investigations targeting AhR ligands, the precise physiological role of AhR remains unknown. Therefore, we explored novel AhR target genes and identified CC-chemokine ligand 5 (CCL5), a key mediator in the development of inflammatory responses. AhR ligands, such as 6-formylindolo[3,2-b]carbazole (FICZ) and benzo[a]pyrene (BaP), significantly reduced CCL5 mRNA and protein expression in HaCaT cells. These effects were observed in normal human epidermal keratinocytes (NHEKs) and mouse primary keratinocytes. AhR knockdown with siRNA restored CCL5 inhibition by AhR ligands. In addition, AhR ligands exhibited a dose-dependent suppression of CCL5 production induced by Th1-derived cytokines. Our findings indicate that AhR ligands would inhibit to some extent the infiltration of inflammatory cells.
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