このエントリーをはてなブックマークに追加
ID 56672
FullText URL
Author
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
Abstract
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.
Published Date
2016-04-07
Publication Title
Nucleic Acids Research
Volume
volume44
Issue
issue12
Publisher
Oxford University Press
Start Page
5658
End Page
5672
ISSN
03051048
NCID
AA00760269
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
File Version
publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1093/nar/gkw189
Project
Collaborative Research of Okayama University for Infectious Diseases in India