Role of Macrophage CCAAT/Enhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice

Ling Hua Chang, Huei-Sheng Huang, Po-Ting Wu, I. Ming Jou, Min Hsiung Pan, Wen Chang Chang, Dennis Ding Hwa Wang, Ju-Ming Wang

研究成果: Article

21 引文 (Scopus)

摘要

Background: The up-regulation of CCAAT/enhancer binding protein delta (CEBPD) has frequently been observed in macrophages in age-associated disorders, including rheumatoid arthritis (RA). However, the role of macrophage CEBPD in the pathogenesis of RA is unclear. Methodology and Principal Findings: We found that the collagen-induced arthritis (CIA) score and the number of affected paws in Cebpd -/- mice were significantly decreased compared with the wild-type (WT) mice. The histological analysis revealed an attenuated CIA in Cebpd -/- mice, as shown by reduced pannus formation and greater integrity of joint architecture in affected paws of Cebpd -/- mice compared with WT mice. In addition, immunohistochemistry analysis revealed decreased pannus proliferation and angiogenesis in Cebpd -/- mice compared with WT mice. CEBPD activated in macrophages played a functional role in promoting the tube formation of endothelial cells and the migration and proliferation of synoviocytes. In vivo DNA binding assays and reporter assays showed that CEBPD up-regulated CCL20, CXCL1, IL23A and TNFAIP6 transcripts through direct binding to their promoter regions. CCL20, IL23A, CXCL1 and TNFAIP6 contributed to the migration and proliferation of synoviocytes, and the latter two proteins were involved in tube formation of endothelial cells. Finally, two anti-inflammatory chemicals, inotilone and rosmanol, reduced the expression of CEBPD and its downstream targets and mitigated the above phenomena. Conclusions and Significance: Collectively, our findings suggest that CEBPD and its downstream effectors could be biomarkers for the diagnosis of RA and potentially serve as therapeutic targets for RA therapy.

原文English
文章編號e45378
期刊PloS one
7
發行號9
DOIs
出版狀態Published - 2012 九月 24

指紋

CCAAT-Enhancer-Binding Protein-delta
Experimental Arthritis
rheumatoid arthritis
Macrophages
arthritis
collagen
binding proteins
Rheumatoid Arthritis
macrophages
Collagen
pathogenesis
mice
Endothelial cells
Assays
endothelial cells
Endothelial Cells
Biomarkers
therapeutics
Genetic Promoter Regions
assays

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

引用此文

@article{8a0143860b854d6286f691a315543a9a,
title = "Role of Macrophage CCAAT/Enhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice",
abstract = "Background: The up-regulation of CCAAT/enhancer binding protein delta (CEBPD) has frequently been observed in macrophages in age-associated disorders, including rheumatoid arthritis (RA). However, the role of macrophage CEBPD in the pathogenesis of RA is unclear. Methodology and Principal Findings: We found that the collagen-induced arthritis (CIA) score and the number of affected paws in Cebpd -/- mice were significantly decreased compared with the wild-type (WT) mice. The histological analysis revealed an attenuated CIA in Cebpd -/- mice, as shown by reduced pannus formation and greater integrity of joint architecture in affected paws of Cebpd -/- mice compared with WT mice. In addition, immunohistochemistry analysis revealed decreased pannus proliferation and angiogenesis in Cebpd -/- mice compared with WT mice. CEBPD activated in macrophages played a functional role in promoting the tube formation of endothelial cells and the migration and proliferation of synoviocytes. In vivo DNA binding assays and reporter assays showed that CEBPD up-regulated CCL20, CXCL1, IL23A and TNFAIP6 transcripts through direct binding to their promoter regions. CCL20, IL23A, CXCL1 and TNFAIP6 contributed to the migration and proliferation of synoviocytes, and the latter two proteins were involved in tube formation of endothelial cells. Finally, two anti-inflammatory chemicals, inotilone and rosmanol, reduced the expression of CEBPD and its downstream targets and mitigated the above phenomena. Conclusions and Significance: Collectively, our findings suggest that CEBPD and its downstream effectors could be biomarkers for the diagnosis of RA and potentially serve as therapeutic targets for RA therapy.",
author = "Chang, {Ling Hua} and Huei-Sheng Huang and Po-Ting Wu and Jou, {I. Ming} and Pan, {Min Hsiung} and Chang, {Wen Chang} and Wang, {Dennis Ding Hwa} and Ju-Ming Wang",
year = "2012",
month = "9",
day = "24",
doi = "10.1371/journal.pone.0045378",
language = "English",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "9",

}

Role of Macrophage CCAAT/Enhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice. / Chang, Ling Hua; Huang, Huei-Sheng; Wu, Po-Ting; Jou, I. Ming; Pan, Min Hsiung; Chang, Wen Chang; Wang, Dennis Ding Hwa; Wang, Ju-Ming.

於: PloS one, 卷 7, 編號 9, e45378, 24.09.2012.

研究成果: Article

TY - JOUR

T1 - Role of Macrophage CCAAT/Enhancer Binding Protein Delta in the Pathogenesis of Rheumatoid Arthritis in Collagen-Induced Arthritic Mice

AU - Chang, Ling Hua

AU - Huang, Huei-Sheng

AU - Wu, Po-Ting

AU - Jou, I. Ming

AU - Pan, Min Hsiung

AU - Chang, Wen Chang

AU - Wang, Dennis Ding Hwa

AU - Wang, Ju-Ming

PY - 2012/9/24

Y1 - 2012/9/24

N2 - Background: The up-regulation of CCAAT/enhancer binding protein delta (CEBPD) has frequently been observed in macrophages in age-associated disorders, including rheumatoid arthritis (RA). However, the role of macrophage CEBPD in the pathogenesis of RA is unclear. Methodology and Principal Findings: We found that the collagen-induced arthritis (CIA) score and the number of affected paws in Cebpd -/- mice were significantly decreased compared with the wild-type (WT) mice. The histological analysis revealed an attenuated CIA in Cebpd -/- mice, as shown by reduced pannus formation and greater integrity of joint architecture in affected paws of Cebpd -/- mice compared with WT mice. In addition, immunohistochemistry analysis revealed decreased pannus proliferation and angiogenesis in Cebpd -/- mice compared with WT mice. CEBPD activated in macrophages played a functional role in promoting the tube formation of endothelial cells and the migration and proliferation of synoviocytes. In vivo DNA binding assays and reporter assays showed that CEBPD up-regulated CCL20, CXCL1, IL23A and TNFAIP6 transcripts through direct binding to their promoter regions. CCL20, IL23A, CXCL1 and TNFAIP6 contributed to the migration and proliferation of synoviocytes, and the latter two proteins were involved in tube formation of endothelial cells. Finally, two anti-inflammatory chemicals, inotilone and rosmanol, reduced the expression of CEBPD and its downstream targets and mitigated the above phenomena. Conclusions and Significance: Collectively, our findings suggest that CEBPD and its downstream effectors could be biomarkers for the diagnosis of RA and potentially serve as therapeutic targets for RA therapy.

AB - Background: The up-regulation of CCAAT/enhancer binding protein delta (CEBPD) has frequently been observed in macrophages in age-associated disorders, including rheumatoid arthritis (RA). However, the role of macrophage CEBPD in the pathogenesis of RA is unclear. Methodology and Principal Findings: We found that the collagen-induced arthritis (CIA) score and the number of affected paws in Cebpd -/- mice were significantly decreased compared with the wild-type (WT) mice. The histological analysis revealed an attenuated CIA in Cebpd -/- mice, as shown by reduced pannus formation and greater integrity of joint architecture in affected paws of Cebpd -/- mice compared with WT mice. In addition, immunohistochemistry analysis revealed decreased pannus proliferation and angiogenesis in Cebpd -/- mice compared with WT mice. CEBPD activated in macrophages played a functional role in promoting the tube formation of endothelial cells and the migration and proliferation of synoviocytes. In vivo DNA binding assays and reporter assays showed that CEBPD up-regulated CCL20, CXCL1, IL23A and TNFAIP6 transcripts through direct binding to their promoter regions. CCL20, IL23A, CXCL1 and TNFAIP6 contributed to the migration and proliferation of synoviocytes, and the latter two proteins were involved in tube formation of endothelial cells. Finally, two anti-inflammatory chemicals, inotilone and rosmanol, reduced the expression of CEBPD and its downstream targets and mitigated the above phenomena. Conclusions and Significance: Collectively, our findings suggest that CEBPD and its downstream effectors could be biomarkers for the diagnosis of RA and potentially serve as therapeutic targets for RA therapy.

UR - http://www.scopus.com/inward/record.url?scp=84866720745&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866720745&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0045378

DO - 10.1371/journal.pone.0045378

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 9

M1 - e45378

ER -