TLR4 expression in mouse embryonic stem cells and in stem cell-derived vascular cells is regulated by epigenetic modifications

A Zampetaki; Q Z Xiao; L F Zeng; Y H Hu; Q B Xu

doi:10.1016/j.bbrc.2006.06.055

TLR4 expression in mouse embryonic stem cells and in stem cell-derived vascular cells is regulated by epigenetic modifications

A Zampetaki, Q Z Xiao, L F Zeng, Y H Hu, Q B Xu

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

52 Citations (Scopus)

Abstract

Embryonic stem (ES) cells and ES cell-derived differentiated cells can be used in tissue regeneration approaches. However, inflammation may pose a major hurdle. To define the inflammatory response of ES and ES cell-derived vascular cells, we exposed these cells to LPS. With the exception of MIF no significant cytokine mRNA levels were observed either at baseline or after stimulation. Further experiments revealed that these cells do not express TLR4. Analysis of the DNA methylation status of the TLR4 upstream region showed increased methylation. Moreover, in vitro methylation suppressed TLR4 promoter activity in reporter gene assays. ChIP assays showed that in this region histories H3 and H4 are hypoacetylated in ES cells. Interestingly, 5-aza-dC or TSA partially relieves this gene repression. Finally, the increased levels of TLR4 observed in ES cells after treatment with 5-aza-dC or TSA confer responsiveness to LPS, as induction of IL-6 and TNF alpha mRNA was detected in endotoxin stimulated ES cells. (c) 2006 Elsevier Inc. All rights reserved

Original language	English
Pages (from-to)	89 - 99
Number of pages	11
Journal	Biochemical and Biophysical Research Communications
Volume	347
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2006.06.055
Publication status	Published - 18 Aug 2006

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title = "TLR4 expression in mouse embryonic stem cells and in stem cell-derived vascular cells is regulated by epigenetic modifications",

abstract = "Embryonic stem (ES) cells and ES cell-derived differentiated cells can be used in tissue regeneration approaches. However, inflammation may pose a major hurdle. To define the inflammatory response of ES and ES cell-derived vascular cells, we exposed these cells to LPS. With the exception of MIF no significant cytokine mRNA levels were observed either at baseline or after stimulation. Further experiments revealed that these cells do not express TLR4. Analysis of the DNA methylation status of the TLR4 upstream region showed increased methylation. Moreover, in vitro methylation suppressed TLR4 promoter activity in reporter gene assays. ChIP assays showed that in this region histories H3 and H4 are hypoacetylated in ES cells. Interestingly, 5-aza-dC or TSA partially relieves this gene repression. Finally, the increased levels of TLR4 observed in ES cells after treatment with 5-aza-dC or TSA confer responsiveness to LPS, as induction of IL-6 and TNF alpha mRNA was detected in endotoxin stimulated ES cells. (c) 2006 Elsevier Inc. All rights reserved",

author = "A Zampetaki and Xiao, {Q Z} and Zeng, {L F} and Hu, {Y H} and Xu, {Q B}",

year = "2006",

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T1 - TLR4 expression in mouse embryonic stem cells and in stem cell-derived vascular cells is regulated by epigenetic modifications

AU - Zampetaki, A

AU - Xiao, Q Z

AU - Zeng, L F

AU - Hu, Y H

AU - Xu, Q B

PY - 2006/8/18

Y1 - 2006/8/18

N2 - Embryonic stem (ES) cells and ES cell-derived differentiated cells can be used in tissue regeneration approaches. However, inflammation may pose a major hurdle. To define the inflammatory response of ES and ES cell-derived vascular cells, we exposed these cells to LPS. With the exception of MIF no significant cytokine mRNA levels were observed either at baseline or after stimulation. Further experiments revealed that these cells do not express TLR4. Analysis of the DNA methylation status of the TLR4 upstream region showed increased methylation. Moreover, in vitro methylation suppressed TLR4 promoter activity in reporter gene assays. ChIP assays showed that in this region histories H3 and H4 are hypoacetylated in ES cells. Interestingly, 5-aza-dC or TSA partially relieves this gene repression. Finally, the increased levels of TLR4 observed in ES cells after treatment with 5-aza-dC or TSA confer responsiveness to LPS, as induction of IL-6 and TNF alpha mRNA was detected in endotoxin stimulated ES cells. (c) 2006 Elsevier Inc. All rights reserved

AB - Embryonic stem (ES) cells and ES cell-derived differentiated cells can be used in tissue regeneration approaches. However, inflammation may pose a major hurdle. To define the inflammatory response of ES and ES cell-derived vascular cells, we exposed these cells to LPS. With the exception of MIF no significant cytokine mRNA levels were observed either at baseline or after stimulation. Further experiments revealed that these cells do not express TLR4. Analysis of the DNA methylation status of the TLR4 upstream region showed increased methylation. Moreover, in vitro methylation suppressed TLR4 promoter activity in reporter gene assays. ChIP assays showed that in this region histories H3 and H4 are hypoacetylated in ES cells. Interestingly, 5-aza-dC or TSA partially relieves this gene repression. Finally, the increased levels of TLR4 observed in ES cells after treatment with 5-aza-dC or TSA confer responsiveness to LPS, as induction of IL-6 and TNF alpha mRNA was detected in endotoxin stimulated ES cells. (c) 2006 Elsevier Inc. All rights reserved

U2 - 10.1016/j.bbrc.2006.06.055

DO - 10.1016/j.bbrc.2006.06.055

M3 - Article

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EP - 99

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

IS - 1

ER -

TLR4 expression in mouse embryonic stem cells and in stem cell-derived vascular cells is regulated by epigenetic modifications

Abstract

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