LPS-induced inflammatory response is suppressed by Wnt inhibitors, Dickkopf-1 and LGK974

Jang, Jaewoong; Jung, Yoonju; Kim, Youngeun; Jho, Eek‐hoon; Yoon, Yoosik

doi:10.1038/srep41612

Cited by 74 publications

(64 citation statements)

References 43 publications

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“…In this study, IL‐1β expression in the infected macrophages was dependent on Wnt5a. Similar to our research, Jang J et al found that Wnt5a knockdown suppressed LPS‐induced IL‐1β and IL‐6 expression in human bronchial epithelial cells or umbilical vein endothelial cells, and Wu T et al found that nucleoside reverse transcriptase inhibitors up‐regulated IL‐1β, TNF‐α, and IL‐6 in a Wnt5a dependent manner in the central nervous system. Taken together, these observations are consistent with our results that Wnt5a is also involved in the expression of IL‐1β in host immune response.…”

Section: Discussionsupporting

confidence: 90%

Wnt5a is involved in LOX‐1 and TLR4 induced host inflammatory response in peri‐implantitis

Zhang

Liu

et al. 2019

J of Periodontal Research

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Background and objective Peri‐implantitis is a plaque‐associated pathological condition occurring in tissues around dental implants, characterized by inflammation in the peri‐implant mucosa and subsequent progressive loss of supporting bone. Wnt5a is the activating ligand of the non‐canonical Wnt signaling pathways and plays important roles in leukocyte infiltration and cytokine/ chemokine production in inflammatory disorders. Previous studies showed that Wnt5a was significantly up‐regulated in gingival tissues of chronic and aggressive periodontitis. However, the roles and the regulatory mechanisms of Wnt5a in peri‐implantitis are not well known. Methods The expression of Wnt5a in gingival tissues collected from 8 healthy implant patients and 8 peri‐implantitis patients was analyzed by Western blotting and immunofluorescence. Porphyromonas gingivalis infected macrophages isolated from the peripheral blood of healthy volunteers were used as an in vitro cellular model of peri‐implantitis. Using neutralizing antibodies, inhibitors and siRNA, the production and roles of Wnt5a in peri‐implantitis were assessed by immunofluorescence, quantitative polymerase chain reaction (RT‐PCR) and Western blotting. Unpaired two‐tailed Student's t test was used to compare qRT‐PCR and Western blotting results. P ≤ .05 was considered statistically significant. Results Wnt5a was highly expressed in the gingival tissues of peri‐implantitis patients. Compared to controls, Wnt5a increased in P gingivalis infected macrophages. Wnt5a production in response to P gingivalis infection was dependent on LOX‐1 and TLR4. Compared to controls, Wnt5a knockdown impaired IL‐1β, MCP‐1, and MMP2 production induced by P gingivalis infection. Conclusion Our results indicate that Wnt5a is involved in LOX‐1 and TLR4 induced inflammatory signature via inflammatory cytokines production in response to P gingivalis infection. These findings demonstrate that Wnt5a maybe an important component of the host immune response in peri‐implantitis.

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Section: Discussionsupporting

confidence: 90%

Wnt5a is involved in LOX‐1 and TLR4 induced host inflammatory response in peri‐implantitis

Zhang

Liu

et al. 2019

J of Periodontal Research

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“…This study showed that high-glucose culture for 3 days reduced HUVEC viability and NO production, but the damage could be significantly relieved after intervention with OMT or A 2B siRNA. This study has revealed that the expressions of pro-inflammatory genes including TNF-α, IL-6 and IL-1β were increased by LPS-induced inflammatory response in HUVECs [34]. In this study, the results also revealed that IL-1β and TNF-α levels increased significantly due to high glucose, and that OMT could reverse Fig.…”

Section: Discussionsupporting

confidence: 68%

Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

Shen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Diabetes mellitus (DM) has become an increasingly epidemic metabolic disease. Vascular endothelial cells play a key role in developing the cardiovascular complications of DM. The A 2B receptor is expressed in vascular endothelial cells, and may help regulate the function of endothelial cells. The aim of this study was to investigate the protective effects of oxymatrine (OMT) on human umbilical vein endothelial cells (HUVECs) from high glucoseinduced cytotoxicity. Methods: Homology modeling and molecular docking analysis were used to detect the binding sites between the adenosine A 2B receptor and OMT. HUVECs were cultured with control (5.5 mM) or elevated glucose (22.2 mM) in the presence or absence of 3 µM OMT or A 2B siRNA for 3 days. The MTS cell viability assay was used to measure the toxicity of high glucose on HUVECs and the protective effect of OMT or A 2B siRNA. The expression of the adenosine A 2B receptor and CCL5 in HUVECs was detected with real-time quantitative PCR (qPCR) and Western blotting methods in each group. Levels of IL-1β and TNF-α were measured using an enzyme-linked immunosorbent assay (ELISA) kit, and the concentration of NO was detected with the nitrate reductase method. Monocyte chemotactic activity in each group was detected using Transwell chambers. Furthermore, the phosphorylation of p38 and ERK1/2 in each group was observed through the Western blotting method. Results: Homology modeling and molecular docking analysis showed that OMT contains well-fitted binding sites to the A 2B receptor. After chronic culture at high glucose, the rate of cell viability was significantly lower than that of the control group. After co-treatment with OMT or A 2B siRNA, cell viability was significantly increased compared with the high-glucose group. The results from real-time quantitative RT-PCR (qRT-PCR) and Western blotting indicated that high glucose could increase the expression of A 2B receptors in HUVECs, an effect that was inhibited by OMT. In addition, the results revealed that the expression of CCL5, IL-1β and TNF-α was increased in the high-glucose group, and that the NO produced by HUVECs decreased due to hyperglycemia; however, co-culture with OMT or A 2B siRNA abolished these effects. Meanwhile, the chemotaxis activity of monocytes to HUVECs cultured in high-glucose medium was enhanced 2.59-fold compared to the control cells. However, the inflammatory reactions in HUVECs were completely relieved by co-treatment with OMT or A 2B siRNA. Moreover, the phosphorylation of p38 and ERK1/2 in HUVECs in the high-glucose group was significantly higher than that of the control group; these effects were reversed after co-treatment with OMT or A 2B siRNA. Conclusion: OMT may protect the HUVECs from high glucose-induced cytotoxicity through inhibitting the expression of A 2B receptor and inflammatory factors as well as decreasing the phosphorylation of p38 and ERK1/2.

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“…A state‐of‐the‐art HUVECs‐based an angiogenic assay was used as a benchmark to test how dynamic culture conditions would impact cell behavior. Indeed, HUVECs can be isolated and maintained by standard protocol with relatively minimal requirements (Baudin, Bruneel, Bosselut, & Vaubourdolle, ; Marin, Kaplanski, Grès, Farnarier, & Bongrand, ) and have been shown responsive to physiological and/or pathological stimuli such as high glucose, lipopolysaccharide (LPS) and shear stress (Jang, Jung, Kim, Jho, & Yoon, ; Patel, Chen, Das, & Kavdia, ; Walshe, dela Paz, & D'Amore, ), thus offering a suitable, general model for endothelial cell both in normal and pathological conditions.…”

Section: Resultsmentioning

confidence: 99%

“…An uneven waste concentration distribution within the medium volume, with higher concentration close to the cell-medium interface was apparent in the static condition; on the other hand uniform waste concentrations/ distributions are obtained in the whole medium volume in the dynamic condition.3.1 | Effect of the dynamic cell culture platform over cell functionalityA state-of-the-art HUVECs-based an angiogenic assay was used as a benchmark to test how dynamic culture conditions would impact cell behavior. Indeed, HUVECs can be isolated and maintained by standard protocol with relatively minimal requirements(Baudin, Bruneel, Bosselut, & Vaubourdolle, 2007;Marin, Kaplanski, Grès, Farnarier, & Bongrand, 2001) and have been shown responsive to physiological and/or pathological stimuli such as high glucose, lipopolysaccharide (LPS) and shear stress(Jang, Jung, Kim, Jho, & Yoon, 2017;Patel, Chen, Das, & Kavdia, 2013;Walshe, dela Paz, & D'Amore, 2013), thus offering a suitable, general model for endothelial cell both in normal and pathological conditions.…”

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confidence: 99%

A dynamic culture platform enhances the efficiency of the 3D HUVEC‐based tube formation assay

Lovecchio

Pannella

Giardino

et al. 2019

Biotech & Bioengineering

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Cell-based in vitro biological models traditionally use monolayer cell cultures grown over plastic surfaces bathing in static media. Higher fidelity to a natural biological tissue is expected to result from growing the cells in a three-dimensional (3D) matrix.However, due to the decreased rate of diffusion inherent to increased distances within a tridimensional space, proper fluidic conditions are needed in this setting to better approximate a physiological environment. To this aim, we here propose a prototypal dynamic cell culture platform for the automatic medium replacement, via periodic perfusion flow, in a human umbilical vein endothelial cell (HUVECs) culture seeded in a Geltrex™ matrix. A state-of-the-art angiogenesis assay performed in these dynamic conditions showed sizable effects with respect to conventional static control cultures, with significantly enhanced pro-(dual antiplatelet therapy [DAPT]) and anti-(EDTA) angiogenic compound activity. In particular, dynamic culture conditions (a) enhance the 3D-organization of HUVECs into microtubule structure; (b) accelerate and improve endothelial tube formation by HUVECs in the presence of DAPT; (c) are able to completely revert the blocking effects of EDTA. These evidence emphasize the need of setting proper fluidic conditions for a better approximation of a physiological environment as an appropriate evolution of current cell culture paradigms. K E Y W O R D S Bioreactor system, drug discovery, finite element modeling, HUVECs, periodic perfusion, tube formation assay

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LPS-induced inflammatory response is suppressed by Wnt inhibitors, Dickkopf-1 and LGK974

Cited by 74 publications

References 43 publications

Wnt5a is involved in LOX‐1 and TLR4 induced host inflammatory response in peri‐implantitis

Wnt5a is involved in LOX‐1 and TLR4 induced host inflammatory response in peri‐implantitis

Protective Effects of Oxymatrine on Vascular Endothelial Cells from High-Glucose-Induced Cytotoxicity by Inhibiting the Expression of A2B Receptor

A dynamic culture platform enhances the efficiency of the 3D HUVEC‐based tube formation assay

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