Transcriptional regulation of the novel Toll-like receptor Tlr13.
Little has been known about Tlr13 (Toll-like receptor 13), a novel member of the Toll-like receptor family. To elucidate the molecular basis of murine Tlr13 gene expression, the activity of the Tlr13 gene promoter was characterized. Reporter gene analysis and electrophoretic mobility shift assays demonstrated that Tlr13 gene transcription was regulated through three cis-acting elements that interacted with the Ets2, Sp1, and PU.1 transcription factors. Furthermore, our work suggests that these transcription factors may cooperate, culminating in maximal transcription of the Tlr13 gene. In contrast, NF-kappaB appeared to act as an inhibitor of Tlr13 transcription. Overexpression of Ets2 caused a strong increase in the transcriptional activity of the Tlr13 promoter; however, overexpression of NF-kappaB p65 dramatically inhibited it. Additionally, interferon-beta is capable of acting Tlr13 transcription, but the activated signaling of lipopolysaccharide/TLR4 and peptidoglycan/TLR2 strongly inhibited the Tlr13 gene promoter. Thus, these findings reveal the mechanism of Tlr13 gene regulation, thereby providing insight into the function of Tlr13 in the immune response to pathogen.
Shi
Zhongcheng
Z
Center for Infectious and Inflammatory Disease, Institute of Bioscience and Technology, Texas A&M University Health Science Center, Houston, Texas 77030, USA.
Cai
Zhenyu
Z
Wen
Shu
S
Chen
Caoyi
C
Gendron
Christi
C
Sanchez
Amir
A
Patterson
Kevin
K
Fu
Songbin
S
Yang
Jianhua
J
Wildman
Derek
D
Finnell
Richard H
RH
Zhang
Dekai
D
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D050787:Proto-Oncogene Protein c-ets-2 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D051193:Toll-Like Receptors / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000187:drug effects; D000099232:Proto-Oncogene Protein Spi-1
D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011070:Poly I-C; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C539093:Tlr13 protein, mouse