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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
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.
発行日
2016-04-07
出版物タイトル
Nucleic Acids Research
44巻
12号
出版者
Oxford University Press
開始ページ
5658
終了ページ
5672
ISSN
03051048
NCID
AA00760269
資料タイプ
学術雑誌論文
言語
English
OAI-PMH Set
岡山大学
論文のバージョン
publisher
PubMed ID
DOI
Web of Science KeyUT
関連URL
isVersionOf https://doi.org/10.1093/nar/gkw189
プロジェクト
インド感染症共同研究