Activation of GATA‐binding protein 4 regulates monocyte chemoattractant protein‐1 and chemotaxis in periodontal ligament cells

Abstract

Background and Objectives Periodontitis is a chronic inflammatory disease of periodontal supporting tissues. The persistent inflammatory reaction depends on the release of chemokines to continuously recruit inflammation cells. GATA‐binding protein 4 (GATA4) exerts effects on senescence and inflammation, while its role in periodontitis is far from clear. The present study aims to address the effect of GATA4 on regulating chemokines and the chemotaxis in periodontitis. Material and Methods Periodontitis rat models were constructed to detect the expression of GATA4 and the chemokine monocyte chemoattractant protein‐1 (MCP‐1) by immunohistochemistry. Lipopolysaccharide (LPS)‐stimulated human periodontal ligament (PDL) cells and GATA4‐knockdown by siRNA transient transfection PDL cells were used to explore the correlation between GATA4 and chemokines. Transwell assay was performed to detect the role of GATA4 for the recruitment effect of chemokines on macrophages. Mitogen‐activated protein kinase (MAPK) inhibitors were scheduled to intervene in LPS‐stimulated PDL cells to examine the association between MAPK signaling pathways and GATA4. The expression of GATA4, chemokines, or MAPK signaling molecules was determined by quantitative real‐time polymerase chain reaction, western blotting, or cell immunofluorescence. Results The expression of GATA4 and MCP‐1 was significantly increased in periodontitis rat models and in LPS‐stimulated PDL cells. Knockdown GATA4 inhibited the expression of GATA4 and MCP‐1 as well as suppressed the recruitment of macrophage in LPS‐stimulated PDL cells. Inhibitors of p38 and ERK1/2 signaling pathways significantly downregulated the increased expression of GATA4 and MCP‐1 induced by LPS in PDL cells. Conclusions GATA‐binding protein 4 could act as an upstream regulator of MCP‐1 and as a downstream regulator of p38 and ERK1/2 signaling pathways to initiate inflammation response and regulate chemotaxis during the progression of periodontitis.

Chemokines in Periodontal Diseases

“…The initiation of periodontal disease is due to bacterial infection [2]. Normally, periodontal tissue is highly responsive to oral microbial stimulation with the coordinated release of host defense mediators [24]. Excessive pathogenic bacterial invasion into periodontal tissues disrupts the immune response and causes the release of excessive inflammatory mediators in tissues that will destroy periodontal tissues [24,25].…”

“…Normally, periodontal tissue is highly responsive to oral microbial stimulation with the coordinated release of host defense mediators [24]. Excessive pathogenic bacterial invasion into periodontal tissues disrupts the immune response and causes the release of excessive inflammatory mediators in tissues that will destroy periodontal tissues [24,25]. İnflame periodontal tissue includes an accumulation of T cells, B cells, macrophages, and dendritic cells [3].…”

“…The chemokine (C-C motif) ligand 2 (CCL2) also referred to as monocyte chemoattractant protein 1 (MCP-1), is a strong chemoattractant for monocytes, lymphocytes, natural killers, and macrophages [5,24]. MCP-1 attracts CCR2-and CCR4-positive cells and is linked to Th2 responses [13,35].…”

“…MCP-1 attracts CCR2-and CCR4-positive cells and is linked to Th2 responses [13,35]. Several signaling pathways involved in the increased MCP-1 in inflammatory responses include the NF-κB pathway, TLR2/4 signaling pathway, phosphatidylinositol 3-kinase/Akt pathway, and MAPK signaling pathways [24]. It has been argued that in particular, the MAPK Chemokines in Periodontal Diseases DOI: http://dx.doi.org/10.5772/intechopen.106846 signaling pathway can determine the role of MCP-1 in periodontal diseases, as the MAPK signaling pathway increases MCP-1 production in human gingival fibroblasts [41].…”

“…It has been argued that in particular, the MAPK Chemokines in Periodontal Diseases DOI: http://dx.doi.org/10.5772/intechopen.106846 signaling pathway can determine the role of MCP-1 in periodontal diseases, as the MAPK signaling pathway increases MCP-1 production in human gingival fibroblasts [41]. It has been stated that Gram-negative bacterial LPS, which is one of the most important causes of periodontal diseases, can also activate the MAPK pathway in periodontal tissue cells [24]. However, it showed that MCP-1 could not provide an adequate signal in the epithelial cell response against oral biofilm [38].…”