Transcriptional regulation of Tlr11 gene expression in epithelial cells.
As sensors of invading microorganisms, Toll-like receptors (TLRs) are expressed not only on macrophages and dendritic cells (DCs) but also on epithelial cells. In the TLR family, Tlr11 appears to have the unique feature in that it is expressed primarily on epithelial cells, although it is also expressed on DCs and macrophages. Here, we demonstrate that transcription of the Tlr11 gene is regulated through two cis-acting elements, one Ets-binding site and one interferon regulatory factor (IRF)-binding site. The Ets element interacts with the epithelium-specific transcription factors, ESE-1 and ESE-3, and the IRF motif interacts with IRF-8. Thus, Tlr11 expression on epithelial cells is regulated by the transcription factors that are presumably distinct from transcription factors that regulate the expression of TLRs in innate immune cells such as macrophages and DCs. Our results imply that the distinctive transcription regulatory machinery for TLRs on epithelium may represent a promising new avenue for the development of epithelia-specific therapeutic interventions.
Cai
Zhenyu
Z
Center for Infectious and Inflammatory Disease, Institute of Bioscience and Technology, Texas A&M University Health Science Center, USA.
Shi
Zhongcheng
Z
Sanchez
Amir
A
Zhang
Tingting
T
Liu
Mingyao
M
Yang
Jianghua
J
Wang
Fen
F
Zhang
Dekai
D
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D014162:Transfection; D000099185:Interferon Regulatory Factor-8
D050835:Interferon Regulatory Factors; D034741:RNA, Small Interfering; D051193:Toll-Like Receptors; D014157:Transcription Factors; D000099185:Interferon Regulatory Factor-8; C482902:TLR11 protein, human