Cargando…
CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway
BACKGROUND: Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. CTGF is abundantly expressed in osteoarthritis (OA). However, the relationship between CTGF and IL-6 in OA synovial fib...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515445/ https://www.ncbi.nlm.nih.gov/pubmed/23227240 http://dx.doi.org/10.1371/journal.pone.0051097 |
_version_ | 1782252182158966784 |
---|---|
author | Liu, Shan-Chi Hsu, Chin-Jung Chen, Hsien-Te Tsou, Hsi-Kai Chuang, Show-Mei Tang, Chih-Hsin |
author_facet | Liu, Shan-Chi Hsu, Chin-Jung Chen, Hsien-Te Tsou, Hsi-Kai Chuang, Show-Mei Tang, Chih-Hsin |
author_sort | Liu, Shan-Chi |
collection | PubMed |
description | BACKGROUND: Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. CTGF is abundantly expressed in osteoarthritis (OA). However, the relationship between CTGF and IL-6 in OA synovial fibroblasts (OASFs) is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: OASFs showed significant expression of CTGF, and expression was higher than in normal SFs. OASFs stimulation with CTGF induced concentration-dependent increases in IL-6 expression. CTGF mediated IL-6 production was attenuated by αvβ5 integrin neutralized antibody and apoptosis signal-regulating kinase 1 (ASK1) shRNA. Pretreatment with p38 inhibitor (SB203580), JNK inhibitor (SP600125), AP-1 inhibitors (Curcumin and Tanshinone IIA), and NF-κB inhibitors (PDTC and TPCK) also inhibited the potentiating action of CTGF. CTGF-mediated increase of NF-κB and AP-1 luciferase activity was inhibited by SB203580 and SP600125 or ASK1 shRNA or p38 and JNK mutant. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CTGF increased IL-6 production in OASFs via the αvβ5 integrin, ASK1, p38/JNK, and AP-1/NF-κB signaling pathways. |
format | Online Article Text |
id | pubmed-3515445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35154452012-12-07 CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway Liu, Shan-Chi Hsu, Chin-Jung Chen, Hsien-Te Tsou, Hsi-Kai Chuang, Show-Mei Tang, Chih-Hsin PLoS One Research Article BACKGROUND: Connective tissue growth factor (CTGF; also known as CCN2) is an inflammatory mediator, and shows elevated levels in regions of severe injury and inflammatory diseases. CTGF is abundantly expressed in osteoarthritis (OA). However, the relationship between CTGF and IL-6 in OA synovial fibroblasts (OASFs) is mostly unknown. METHODOLOGY/PRINCIPAL FINDINGS: OASFs showed significant expression of CTGF, and expression was higher than in normal SFs. OASFs stimulation with CTGF induced concentration-dependent increases in IL-6 expression. CTGF mediated IL-6 production was attenuated by αvβ5 integrin neutralized antibody and apoptosis signal-regulating kinase 1 (ASK1) shRNA. Pretreatment with p38 inhibitor (SB203580), JNK inhibitor (SP600125), AP-1 inhibitors (Curcumin and Tanshinone IIA), and NF-κB inhibitors (PDTC and TPCK) also inhibited the potentiating action of CTGF. CTGF-mediated increase of NF-κB and AP-1 luciferase activity was inhibited by SB203580 and SP600125 or ASK1 shRNA or p38 and JNK mutant. CONCLUSIONS/SIGNIFICANCE: Our results suggest that CTGF increased IL-6 production in OASFs via the αvβ5 integrin, ASK1, p38/JNK, and AP-1/NF-κB signaling pathways. Public Library of Science 2012-12-05 /pmc/articles/PMC3515445/ /pubmed/23227240 http://dx.doi.org/10.1371/journal.pone.0051097 Text en © 2012 Liu 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 Liu, Shan-Chi Hsu, Chin-Jung Chen, Hsien-Te Tsou, Hsi-Kai Chuang, Show-Mei Tang, Chih-Hsin CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway |
title | CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway |
title_full | CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway |
title_fullStr | CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway |
title_full_unstemmed | CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway |
title_short | CTGF Increases IL-6 Expression in Human Synovial Fibroblasts through Integrin-Dependent Signaling Pathway |
title_sort | ctgf increases il-6 expression in human synovial fibroblasts through integrin-dependent signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515445/ https://www.ncbi.nlm.nih.gov/pubmed/23227240 http://dx.doi.org/10.1371/journal.pone.0051097 |
work_keys_str_mv | AT liushanchi ctgfincreasesil6expressioninhumansynovialfibroblaststhroughintegrindependentsignalingpathway AT hsuchinjung ctgfincreasesil6expressioninhumansynovialfibroblaststhroughintegrindependentsignalingpathway AT chenhsiente ctgfincreasesil6expressioninhumansynovialfibroblaststhroughintegrindependentsignalingpathway AT tsouhsikai ctgfincreasesil6expressioninhumansynovialfibroblaststhroughintegrindependentsignalingpathway AT chuangshowmei ctgfincreasesil6expressioninhumansynovialfibroblaststhroughintegrindependentsignalingpathway AT tangchihhsin ctgfincreasesil6expressioninhumansynovialfibroblaststhroughintegrindependentsignalingpathway |