ID | 56672 |
フルテキストURL | |
著者 |
Bhupesh Kumar Thakur
Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases
Dasgupta, Nirmalya
Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases
Ta, Atri
Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases
Das, Santasabuj
Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases
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抄録 | Toll-like receptor 5 (TLR5) expression in the intestinal epithelial cells (IECs) is critical to maintain health, as underscored by multiple intestinal and extra-intestinal diseases in mice genetically engineered for IEC-specific TLR5 knockout. A gradient of expression exists in the colonic epithelial cells from the cecum to the distal colon. Intriguingly, an identical gradient for the dietary metabolite, butyrate also exists in the luminal contents. However, both being critical for intestinal homeostasis and immune response, no studies examined the role of butyrate in the regulation of TLR5 expression. We showed that butyrate transcriptionally upregulates TLR5 in the IECs and augments flagellin-induced immune responses. Both basal and butyrate-induced transcription is regulated by differential binding of Sp-family transcription factors to the GC-box sequences over the TLR5 promoter. Butyrate activates two different protein kinase C isoforms to dephosphorylate/acetylate Sp1 by serine/threonine phosphatases and phosphorylate Sp3 by ERK-MAPK, respectively. This resulted in Sp1 displacement from the promoter and binding of Sp3 to it, leading to p300 recruitment and histone acetylation, activating transcription. This is the first study addressing the mechanisms of physiological TLR5 expression in the intestine. Additionally, a novel insight is gained into Sp1/Sp3-mediated gene regulation that may apply to other genes.
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発行日 | 2016-04-07
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出版物タイトル |
Nucleic Acids Research
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巻 | 44巻
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号 | 12号
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出版者 | Oxford University Press
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開始ページ | 5658
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終了ページ | 5672
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ISSN | 03051048
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NCID | AA00760269
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.1093/nar/gkw189
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プロジェクト |
インド感染症共同研究
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