Globular C1q receptor (p33) binds and stabilizes pro-inflammatory MCP-1: a novel mechanism for regulation of MCP-1 production and function

2018 ◽  
Vol 475 (4) ◽  
pp. 775-786 ◽  
Author(s):  
Emma Anders ◽  
Daniel Nebel ◽  
Johannes Westman ◽  
Heiko Herwald ◽  
Bengt-Olof Nilsson ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Periodontal Ligament ◽  
Molecular Mechanisms ◽  
Periodontal Ligament Cells ◽  
Physical Interaction ◽  
Functional Importance ◽  
Vitro Assay ◽  
Human Periodontal Ligament Cells ◽  
And Function ◽  
The Impact

The protein gC1qR (globular C1q receptor), also named p33, was originally identified as a binding partner of the globular heads of C1q in the complement system. gC1qR/p33 is abundantly expressed in many cell types, but the functional importance of this protein is not completely understood. Here, we investigate the impact of gC1qR/p33 on the production and function of the pathophysiologically important chemokine monocyte chemoattractant protein-1 (MCP-1) and the underlying molecular mechanisms. Knockdown of gC1qR/p33 negatively regulated the production of MCP-1, but had no effect on the expression of transcript for MCP-1 in human periodontal ligament cells, suggesting a translational/post-translational mechanism of action. Laser scanning confocal microscopy showed considerable cytosolic co-localization of gC1qR/p33 and MCP-1, and co-immunoprecipitation disclosed direct physical interaction between gC1qR/p33 and MCP-1. Surface plasmon resonance analysis revealed a high-affinity binding (KD = 10.9 nM) between gC1qR/p33 and MCP-1. Using a transwell migration assay, we found that recombinant gC1qR/p33 enhances MCP-1-induced migration of human THP-1 monocytes, pointing to a functional importance of the interaction between gC1qR/p33 and MCP-1. An in vitro assay revealed a rapid turnover of the MCP-1 protein and that gC1qR/p33 stabilizes MCP-1, hence preventing its degradation. We propose that endogenous gC1qR/p33 physically interacts with MCP-1 causing stabilization of the MCP-1 protein and stimulation of its activity in human periodontal ligament cells, suggesting a novel gC1qR/p33-mediated pro-inflammatory mechanism of action.

scholarly journals Intermittent Compressive Stress Enhanced Insulin-Like Growth Factor-1 Expression in Human Periodontal Ligament Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jittima Pumklin ◽  
Jeeranan Manokawinchoke ◽  
Kanokporn Bhalang ◽  
Prasit Pavasant
Keyword(s):  
Mechanical Stress ◽  
Compressive Stress ◽  
Periodontal Ligament ◽  
Molecular Mechanisms ◽  
Treated Group ◽  
Periodontal Ligament Cells ◽  
Human Periodontal Ligament Cells ◽  
Chemical Inhibitors

Mechanical force was shown to promote IGF-1 expression in periodontal ligament both in vitro and in vivo. Though the mechanism of this effect has not yet been proved, here we investigated the molecular mechanism of intermittent mechanical stress on IGF-1 expression. In addition, the role of hypoxia on the intermittent compressive stress on IGF-1 expression was also examined. In this study, human periodontal ligament cells (HPDLs) were stimulated with intermittent mechanical stress for 24 hours. IGF-1 expression was examined by real-time polymerase chain reaction. Chemical inhibitors were used to determine molecular mechanisms of these effects. For hypoxic mimic condition, the CoCl2 supplementation was employed. The results showed that intermittent mechanical stress dramatically increased IGF-1 expression at 24 h. The pretreatment with TGF-β receptor I or TGF-β1 antibody could inhibit the intermittent mechanical stress-induced IGF-1 expression. Moreover, the upregulation of TGF-β1 proteins was detected in intermittent mechanical stress treated group. Correspondingly, the IGF-1 expression was upregulated upon being treated with recombinant human TGF-β1. Further, the hypoxic mimic condition attenuated the intermittent mechanical stress and rhTGF-β1-induced IGF-1 expression. In summary, this study suggests intermittent mechanical stress-induced IGF-1 expression in HPDLs through TGF-β1 and this phenomenon could be inhibited in hypoxic mimic condition.

scholarly journals The Marine-Derived Natural Product Epiloliolide Isolated from Sargassum horneri Regulates NLRP3 via PKA/CREB, Promoting Proliferation and Anti-Inflammatory Effects of Human Periodontal Ligament Cells

Marine Drugs ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. 388
Author(s):  
Eun-Nam Kim ◽  
Woguti Yvonne Nabende ◽  
Hyeyoon Jeong ◽  
Dongyup Hahn ◽  
Gil-Saeng Jeong
Keyword(s):  
Periodontal Ligament ◽  
Treatment Strategies ◽  
Sargassum Horneri ◽  
Periodontal Ligament Cells ◽  
Differentiation Potential ◽  
Proinflammatory Mediators ◽  
Human Periodontal Ligament Cells ◽  
Anti Inflammatory ◽  
The Impact ◽  
Inflammatory Effect

Currently, periodontitis treatment relies on surgical operations, anti-inflammatory agents, or antibiotics. However, these treatments cause pain and side effects, resulting in a poor prognosis. Therefore, in this study, we evaluated the impact of the compound epiloliolide isolated from Sargassum horneri on the recovery of inflammatory inhibitors and loss of periodontal ligaments, which are essential treatment strategies for periodontitis. Here, human periodontal ligament cells stimulated with PG-LPS were treated with the compound epiloliolide, isolated from S. horneri. In the results of this study, epiloliolide proved the anti-inflammatory effect, cell proliferation capacity, and differentiation potential of periodontal ligament cells into osteoblasts, through the regulation of the PKA/CREB signaling pathway. Epiloliolide effectively increased the proliferation and migration of human periodontal ligament cells without cytotoxicity and suppressed the protein expression of proinflammatory mediators and cytokines, such as iNOS, COX-2, TNF-α, IL-6, and IL-1β, by downregulating NLRP3 activated by PG-LPS. Epiloliolide also upregulated the phosphorylation of PKA/CREB proteins, which play an important role in cell growth and proliferation. It was confirmed that the anti-inflammatory effect in PG-LPS-stimulated large cells was due to the regulation of PKA/CREB signaling. We suggest that epiloliolide could serve as a potential novel therapeutic agent for periodontitis by inhibiting inflammation and restoring the loss of periodontal tissue.

scholarly journals The impact of Wnt signalling and hypoxia on osteogenic and cementogenic differentiation in human periodontal ligament cells

2016 ◽  
Vol 14 (6) ◽  
pp. 4975-4982 ◽  
Author(s):  
Shuigen Li ◽  
Jin Shao ◽  
Yinghong Zhou ◽  
Thor Friis ◽  
Jiangwu Yao ◽  
...  
Keyword(s):  
Periodontal Ligament ◽  
Wnt Signalling ◽  
Periodontal Ligament Cells ◽  
Human Periodontal Ligament Cells ◽  
The Impact

scholarly journals Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mechanical Forces ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Development ◽  
And Function ◽  
The Impact

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

GDNF From Human Periodontal Ligament Cells Treated With Pro-Inflammatory Cytokines Promotes Neurocytic Differentiation of PC12 Cells

2016 ◽  
Vol 118 (4) ◽  
pp. 699-708
Author(s):  
Shinichiro Yoshida ◽  
Naohide Yamamoto ◽  
Naohisa Wada ◽  
Atsushi Tomokiyo ◽  
Daigaku Hasegawa ◽  
...  
Keyword(s):  
Pc12 Cells ◽  
Inflammatory Cytokines ◽  
Periodontal Ligament ◽  
Periodontal Ligament Cells ◽  
Human Periodontal Ligament Cells ◽  
Pro Inflammatory Cytokines
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