Unknown,Transcriptomics,Genomics,Proteomics

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Human Toll-Like Receptors Pathway Array Data


ABSTRACT: Endothelial cell (EC) Toll-like receptor 2 (TLR2) activation upregulates the expression of inflammatory mediators and of TLR2 itself, and modulates important endothelial functions, including coagulation and permeability. We defined TLR2 signaling pathways in ECs, and tested the hypothesis that TLR2 signaling differs in ECs and monocytes. We found that ERK5, heretofore unrecognized as mediating TLR2 activation in any cell type, is a central mediator of TLR2-dependent inflammatory signaling in HUVEC, primary human lung microvascular ECs and human monocytes. Additionally, we observed that whereas MEK1 negatively regulates TLR2 signaling in EC, MEK1 promotes TLR2 signaling in monocytes. We also noted that activation of TLR2 led to the upregulation of intracellularly expressed TLR2 and inflammatory mediators via NF-M-NM-:B, JNK and p38-MAPK. Finally, we found that p38-MAPK, JNK, ERK5 and NF-M-NM-:B promote the attachment of human neutrophils to lung microvascular EC that were pretreated with TLR2 agonists. This study newly identifies ERK5 as a key regulator of TLR2 signaling in ECs and monocytes, and indicates that there are fundamental differences in TLR signaling pathways between EC and monocytes. qPCR gene expression profiling. HUVEC monolayers were grown to confluency in EGM-2 media. THP1 suspension cells were grown RPMI 1640 supplemented with 10% FBS, L-glutamine, and antibiotics. Neither cell line was treated with any agonists. RQ values were calculated using the 2-M-NM-^TM-NM-^TCt method. Two biological replicates and one technical replicate were analyzed for both cell lines.

ORGANISM(S): Homo sapiens

SUBMITTER: Kevin Wilhelmsen 

PROVIDER: E-GEOD-33449 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

ERK5 protein promotes, whereas MEK1 protein differentially regulates, the Toll-like receptor 2 protein-dependent activation of human endothelial cells and monocytes.

Wilhelmsen Kevin K   Mesa Kailin R KR   Lucero Jennifer J   Xu Fengyun F   Hellman Judith J  

The Journal of biological chemistry 20120615 32


Endothelial cell (EC) Toll-like receptor 2 (TLR2) activation up-regulates the expression of inflammatory mediators and of TLR2 itself and modulates important endothelial functions, including coagulation and permeability. We defined TLR2 signaling pathways in EC and tested the hypothesis that TLR2 signaling differs in EC and monocytes. We found that ERK5, heretofore unrecognized as mediating TLR2 activation in any cell type, is a central mediator of TLR2-dependent inflammatory signaling in human  ...[more]

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