EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation

Objectives. We aimed to evaluate the effects of Enhancer of Zeste Homolog 2 (EZH2) on regulation of macrophage migration and expression of anti-inflammatory genes in pulpitis. Methods. Dental pulp inflammation was verified by histology in rat pulpitis model induced by lipopolysaccharide (LPS). Immun...

Full description

Saved in:
Bibliographic Details
Main Authors: Ziqi Hu, Yingyi Chen, Jie He, He Liu, Tianqian Hui
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2021/3060480
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832565642964762624
author Ziqi Hu
Yingyi Chen
Jie He
He Liu
Tianqian Hui
author_facet Ziqi Hu
Yingyi Chen
Jie He
He Liu
Tianqian Hui
author_sort Ziqi Hu
collection DOAJ
description Objectives. We aimed to evaluate the effects of Enhancer of Zeste Homolog 2 (EZH2) on regulation of macrophage migration and expression of anti-inflammatory genes in pulpitis. Methods. Dental pulp inflammation was verified by histology in rat pulpitis model induced by lipopolysaccharide (LPS). Immunohistochemistry staining was used to detect changes of the expression of EZH2 and tumor necrosis factor alpha (TNF-α) in dental pulp inflammation. The expression of EZH2, CCL2, and cluster of differentiation 68 (CD68: macrophage surface marker) was measured by immunofluorescence staining. The effect of EZH2 on microphage migration was assessed by cell migration assay. The expressions of anti-inflammatory cytokine interleukins (IL-4 and IL-10) and transforming growth factor-β (TGF-β) in HDPCs which were treated by EZH2 complex, CCL2 complex, and CCL2 antibody were examined by quantitative real-time polymerase chain reaction (q-PCR). Results. The expression of TNF-α gradually increased in dental pulp inflammation. The expression of EZH2 in dental pulp decreased in 8 hours after LPS stimulation. However, the expression of EZH2 gradually increased in dental pulp after 1 day stimulation by LPS. The results of immunofluorescence staining showed that the expressions of EZH2, CCL2, and CD68 were significantly upregulated in dental pulp inflammation of rats. EZH2 could enhance macrophage migration. And the chemotactic activity of macrophages exposed to supernatants of EZH2-treated HDPCs could be inhibited by CCL2 inhibition. In addition, EZH2 suppressed the expression of anti-inflammatory genes, but CCL2 inhibition reversed the downregulation of anti-inflammatory factors, including IL-4 and TGF-β in HDPCs. Conclusions. EZH2 might affect chemotaxis of macrophages and the expression of anti-inflammatory factors by regulating CCL2. EZH2 plays an important role in the development of dental pulp inflammation, and it might be as a target for treatment of pulpitis.
format Article
id doaj-art-4582b76f6f3348c59840211cfce27d1e
institution Kabale University
issn 1687-9678
language English
publishDate 2021-01-01
publisher Wiley
record_format Article
series Stem Cells International
spelling doaj-art-4582b76f6f3348c59840211cfce27d1e2025-02-03T01:07:06ZengWileyStem Cells International1687-96782021-01-01202110.1155/2021/3060480EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp InflammationZiqi Hu0Yingyi Chen1Jie He2He Liu3Tianqian Hui4Department of Pediatric DentistryDepartment of Pediatric DentistryDepartment of Pediatric DentistryDepartment of Pediatric DentistryDepartment of Pediatric DentistryObjectives. We aimed to evaluate the effects of Enhancer of Zeste Homolog 2 (EZH2) on regulation of macrophage migration and expression of anti-inflammatory genes in pulpitis. Methods. Dental pulp inflammation was verified by histology in rat pulpitis model induced by lipopolysaccharide (LPS). Immunohistochemistry staining was used to detect changes of the expression of EZH2 and tumor necrosis factor alpha (TNF-α) in dental pulp inflammation. The expression of EZH2, CCL2, and cluster of differentiation 68 (CD68: macrophage surface marker) was measured by immunofluorescence staining. The effect of EZH2 on microphage migration was assessed by cell migration assay. The expressions of anti-inflammatory cytokine interleukins (IL-4 and IL-10) and transforming growth factor-β (TGF-β) in HDPCs which were treated by EZH2 complex, CCL2 complex, and CCL2 antibody were examined by quantitative real-time polymerase chain reaction (q-PCR). Results. The expression of TNF-α gradually increased in dental pulp inflammation. The expression of EZH2 in dental pulp decreased in 8 hours after LPS stimulation. However, the expression of EZH2 gradually increased in dental pulp after 1 day stimulation by LPS. The results of immunofluorescence staining showed that the expressions of EZH2, CCL2, and CD68 were significantly upregulated in dental pulp inflammation of rats. EZH2 could enhance macrophage migration. And the chemotactic activity of macrophages exposed to supernatants of EZH2-treated HDPCs could be inhibited by CCL2 inhibition. In addition, EZH2 suppressed the expression of anti-inflammatory genes, but CCL2 inhibition reversed the downregulation of anti-inflammatory factors, including IL-4 and TGF-β in HDPCs. Conclusions. EZH2 might affect chemotaxis of macrophages and the expression of anti-inflammatory factors by regulating CCL2. EZH2 plays an important role in the development of dental pulp inflammation, and it might be as a target for treatment of pulpitis.http://dx.doi.org/10.1155/2021/3060480
spellingShingle Ziqi Hu
Yingyi Chen
Jie He
He Liu
Tianqian Hui
EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation
Stem Cells International
title EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation
title_full EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation
title_fullStr EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation
title_full_unstemmed EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation
title_short EZH2 Might Affect Macrophage Chemotaxis and Anti-Inflammatory Factors by Regulating CCL2 in Dental Pulp Inflammation
title_sort ezh2 might affect macrophage chemotaxis and anti inflammatory factors by regulating ccl2 in dental pulp inflammation
url http://dx.doi.org/10.1155/2021/3060480
work_keys_str_mv AT ziqihu ezh2mightaffectmacrophagechemotaxisandantiinflammatoryfactorsbyregulatingccl2indentalpulpinflammation
AT yingyichen ezh2mightaffectmacrophagechemotaxisandantiinflammatoryfactorsbyregulatingccl2indentalpulpinflammation
AT jiehe ezh2mightaffectmacrophagechemotaxisandantiinflammatoryfactorsbyregulatingccl2indentalpulpinflammation
AT heliu ezh2mightaffectmacrophagechemotaxisandantiinflammatoryfactorsbyregulatingccl2indentalpulpinflammation
AT tianqianhui ezh2mightaffectmacrophagechemotaxisandantiinflammatoryfactorsbyregulatingccl2indentalpulpinflammation