Investigation of the expression mechanism of retinoic acid-generating enzyme, RALDH2, which plays key roles in gut immunity

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590106
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tokushima Bunri University
• Principal Investigator: OHOKA Yoshiharu 徳島文理大学, 薬学部, 准教授 (60303971)
• Co-Investigator(Renkei-kenkyūsha): NAKATSUMA Aya (YOKOTA Aya) 徳島文理大学, 香川薬学部, 助教 (30446075)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 腸管免疫 / レチノイン酸 / GM-CSF / Sp1 / RAR / DNAメチル化

Outline of Final Research Achievements

GM-CSF potently induces RALDH2 expression in DCs in an RA-dependent manner, and RA alone weakly induces the expression. In this study, we show that GM-CSF-induced activation of the transcription factor Sp1 and RA-dependent signaling via the RAR/RXR complex contribute to Aldh1a2 expression. The RAR antagonist LE540 and the Sp1 inhibitor mithramycin A inhibited GM-CSF-induced Aldh1a2 expression in Flt3L-generated BM-DCs. Sp1 and the RARα/RXRα complex bound to GC-rich Sp1-binding sites and an RARE half-site, respectively, near the TATA box in the mouse Aldh1a2 promoter. The DNA sequences around these sites were highly conserved among different species. In the presence of RA, ectopic expression of RARα/RXRα and Sp1 synergistically enhanced Aldh1a2 promoter-reporter activity. These results suggest that GM-CSF/RA-induced RALDH2 expression in DCs requires cooperative binding of Sp1 and the RAR/RXR complex to the Aldh1a2 promoter.

Free Research Field

免疫学　生化学　分子生物学