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Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression
Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an i...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928008/ https://www.ncbi.nlm.nih.gov/pubmed/27413250 http://dx.doi.org/10.1155/2016/1062586 |
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author | Luo, Xinjing Chen, Jie Ruan, Jianwei Chen, Yongfeng Mo, Xuanrong Xie, Jiangwen Lv, Guoju |
author_facet | Luo, Xinjing Chen, Jie Ruan, Jianwei Chen, Yongfeng Mo, Xuanrong Xie, Jiangwen Lv, Guoju |
author_sort | Luo, Xinjing |
collection | PubMed |
description | Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients. In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α. |
format | Online Article Text |
id | pubmed-4928008 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-49280082016-07-13 Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression Luo, Xinjing Chen, Jie Ruan, Jianwei Chen, Yongfeng Mo, Xuanrong Xie, Jiangwen Lv, Guoju Mediators Inflamm Research Article Human fibroblast-like synoviocytes play a vital role in joint synovial inflammation in rheumatoid arthritis (RA). Proinflammatory cytokines induce fibroblast-like synoviocyte activation and dysfunction. The inflammatory mediator Krüppel-like factor 4 is upregulated during inflammation and plays an important role in endothelial and macrophage activation during inflammation. However, the role of Krüppel-like factor 4 in fibroblast-like synoviocyte activation and RA inflammation remains to be defined. In this study, we identify the notion that Krüppel-like factor 4 is higher expressed in synovial tissues and fibroblast-like synoviocytes from RA patients than those from osteoarthritis patients. In vitro, the expression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes is induced by proinflammatory cytokine tumor necrosis factor-α. Overexpression of Krüppel-like factor 4 in RA fibroblast-like synoviocytes robustly induced interleukin-6 production in the presence or absence of tumor necrosis factor-α. Conversely, knockdown of Krüppel-like factor 4 markedly attenuated interleukin-6 production in the presence or absence of tumor necrosis factor-α. Krüppel-like factor 4 not only can bind to and activate the interleukin-6 promoter, but also may interact directly with nuclear factor-kappa B. These results suggest that Krüppel-like factor 4 may act as a transcription factor mediating the activation of fibroblast-like synoviocytes in RA by inducing interleukin-6 expression in response to tumor necrosis factor-α. Hindawi Publishing Corporation 2016 2016-06-16 /pmc/articles/PMC4928008/ /pubmed/27413250 http://dx.doi.org/10.1155/2016/1062586 Text en Copyright © 2016 Xinjing Luo et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Luo, Xinjing Chen, Jie Ruan, Jianwei Chen, Yongfeng Mo, Xuanrong Xie, Jiangwen Lv, Guoju Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression |
title | Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression |
title_full | Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression |
title_fullStr | Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression |
title_full_unstemmed | Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression |
title_short | Krüppel-Like Factor 4 Is a Regulator of Proinflammatory Signaling in Fibroblast-Like Synoviocytes through Increased IL-6 Expression |
title_sort | krüppel-like factor 4 is a regulator of proinflammatory signaling in fibroblast-like synoviocytes through increased il-6 expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928008/ https://www.ncbi.nlm.nih.gov/pubmed/27413250 http://dx.doi.org/10.1155/2016/1062586 |
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