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Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B

Inflammation is a multifaceted process: beneficial as a defense mechanism but also detrimental depending on its severity and duration. At the site of injury, inflammatory cells are activated by a cascade of mediators, one of which is LITAF, a transcription regulator known to upregulate TNF-α. We pre...

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Detalles Bibliográficos
Autores principales: Tang, Xiaoren, Yang, Yu, Amar, Salomon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182193/
https://www.ncbi.nlm.nih.gov/pubmed/21980379
http://dx.doi.org/10.1371/journal.pone.0025083
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author Tang, Xiaoren
Yang, Yu
Amar, Salomon
author_facet Tang, Xiaoren
Yang, Yu
Amar, Salomon
author_sort Tang, Xiaoren
collection PubMed
description Inflammation is a multifaceted process: beneficial as a defense mechanism but also detrimental depending on its severity and duration. At the site of injury, inflammatory cells are activated by a cascade of mediators, one of which is LITAF, a transcription regulator known to upregulate TNF-α. We previously showed that human LITAF forms a complex with human STAT6B, which translocates into the nucleus to upregulate cytokine transcription. To dissect the molecular implications of this complex, a murine model was developed and interactions between mouse STAT6B (mSTAT6B) and mouse LITAF (mLITAF) were analyzed. Both mLITAF and mSTAT6B expression were MyD88- and TLR ligand-dependent. Furthermore, mLITAF was found to mediate LPS-induced CCL2 gene transcription with the cooperation of mSTAT6B leading to CCL2 protein expression. In LITAF-deficient mice, mLITAF-mediated CCL2 production in macrophages was significantly reduced compared to the wild-type control animals. Mice knockdown for mSTAT6B by 6BsiRNA1 tail vein injection resulted in a decrease in serum TNF-α and CCL2 production. mLITAF/mSTAT6B complex is proposed to play a role in LPS-induced CCL2 expression and possibly other cytokines.
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spelling pubmed-31821932011-10-06 Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B Tang, Xiaoren Yang, Yu Amar, Salomon PLoS One Research Article Inflammation is a multifaceted process: beneficial as a defense mechanism but also detrimental depending on its severity and duration. At the site of injury, inflammatory cells are activated by a cascade of mediators, one of which is LITAF, a transcription regulator known to upregulate TNF-α. We previously showed that human LITAF forms a complex with human STAT6B, which translocates into the nucleus to upregulate cytokine transcription. To dissect the molecular implications of this complex, a murine model was developed and interactions between mouse STAT6B (mSTAT6B) and mouse LITAF (mLITAF) were analyzed. Both mLITAF and mSTAT6B expression were MyD88- and TLR ligand-dependent. Furthermore, mLITAF was found to mediate LPS-induced CCL2 gene transcription with the cooperation of mSTAT6B leading to CCL2 protein expression. In LITAF-deficient mice, mLITAF-mediated CCL2 production in macrophages was significantly reduced compared to the wild-type control animals. Mice knockdown for mSTAT6B by 6BsiRNA1 tail vein injection resulted in a decrease in serum TNF-α and CCL2 production. mLITAF/mSTAT6B complex is proposed to play a role in LPS-induced CCL2 expression and possibly other cytokines. Public Library of Science 2011-09-28 /pmc/articles/PMC3182193/ /pubmed/21980379 http://dx.doi.org/10.1371/journal.pone.0025083 Text en Tang et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Tang, Xiaoren
Yang, Yu
Amar, Salomon
Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B
title Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B
title_full Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B
title_fullStr Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B
title_full_unstemmed Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B
title_short Novel Regulation of CCL2 Gene Expression by Murine LITAF and STAT6B
title_sort novel regulation of ccl2 gene expression by murine litaf and stat6b
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3182193/
https://www.ncbi.nlm.nih.gov/pubmed/21980379
http://dx.doi.org/10.1371/journal.pone.0025083
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