DJ-1 protein regulates CD3+ T cell migration via overexpression of CXCR4 receptor

Jung, Seung Hyo; Won, Kyung Jong; Lee, Kang Pa; Lee, Dong Hyun; Yu, Suyeol; Lee, Dong-Youb; Seo, Eun‐Hye; Kang, Hyun Jung; Park, Eun-Seok; Kim, Hyun‐Joong; Lee, Seung Hyun; Kim, Bokyung

doi:10.1016/j.atherosclerosis.2014.05.955

Cited by 22 publications

(26 citation statements)

References 41 publications

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“…12G5 clone (targeting the second extracellular loop) and 1D9 clone (targeting the N-terminal receptor portion)] were performed, but also indicated that WZ811 was unable to reduce mAb binding (data not shown). WZ811 was inactive in all of our pharmacological and functional CXCR4 assays in contrast to previous studies that showed inhibition of CXCL12-induced migration/invasion with even greater potency than AMD3100 [22, 38]. Overall, the lack of inhibitory activity of WZ811 in our diverse set of experiments suggests that WZ811 is not, or at least a very weak CXCR4 inhibitor.…”

Section: Discussioncontrasting

confidence: 81%

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

et al. 2017

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The chemokine receptor CXCR4 is activated by its unique chemokine ligand CXCL12 and regulates many physiological and developmental processes such as hematopoietic cell trafficking. CXCR4 is also one of the main co-receptors for human immunodeficiency virus (HIV) entry. Dysfunction of the CXCL12/CXCR4 axis contributes to several human pathologies, including cancer and inflammatory diseases. Consequently, inhibition of CXCR4 activation is recognized as an attractive target for therapeutic intervention. In this regard, numerous agents modifying CXCR4 activity have been evaluated in in vitro experimental studies and pre-clinical models. Here, we evaluated a CXCL12 competition binding assay for its potential as a valuable initial screen for functional and competitive CXCR4 inhibitors. In total, 11 structurally diverse compounds were included in a side-by-side comparison of in vitro CXCR4 cell-based assays, such as CXCL12 competition binding, CXCL12-induced calcium signaling, CXCR4 internalization, CXCL12-guided cell migration and CXCR4-specific HIV-1 replication experiments. Our data indicated that agents that inhibit CXCL12 binding, i.e. the anti-CXCR4 peptide analogs T22, T140 and TC14012 and the small molecule antagonists AMD3100, AMD3465, AMD11070 and IT1t showed inhibitory activity with consistent relative potencies in all further applied CXCR4-related assays. Accordingly, agents exerting no or very weak receptor binding (i.e., CTCE-9908, WZ811, Me6TREN and gambogic acid) showed no or very poor anti-CXCR4 inhibitory activity. Thus, CXCL12 competition binding studies were proven to be highly valuable as an initial screening assay and indicative for the pharmacological and functional profile of competitive CXCR4 antagonists, which will help the design of new potent CXCR4 inhibitors.

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Section: Discussioncontrasting

confidence: 81%

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

et al. 2017

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“…S5). According to previous observations (Jung et al, ), CXCR4 expression was upregulated in DJ‐1 deficient CD4 + T cells cariporide treatment significantly enhanced the expression of CXCR4 in both strains of mice (suppl. Fig.…”

Section: Resultssupporting

confidence: 57%

“…DJ‐1 redox‐sensitive chaperone protein may play a role in the redox regulation of T cell receptor (TCR) signaling. Previous studies suggested that DJ‐1 negatively regulates the expression of chemokine receptor 4 (CXCR4) of stromal cell‐derived factor (SDF)‐1 and T cell migration (Jung et al, ). Therefore, we studied whether protein tyrosine kinase (PTK) activation is involved in ROS production and NHE activation as well as the expression of TCR signaling proteins.…”

Section: Resultsmentioning

confidence: 99%

DJ‐1/Park7 Sensitive Na⁺/H⁺ Exchanger 1 (NHE1) in CD4⁺ T Cells

Zhou

Shi

Chen

et al. 2017

Journal Cellular Physiology

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DJ-1/Park7 is a redox-sensitive chaperone protein counteracting oxidation and presumably contributing to the control of oxidative stress responses and thus inflammation. DJ-1 gene deletion exacerbates the progression of Parkinson's disease presumably by augmenting oxidative stress. Formation of reactive oxygen species (ROS) is paralleled by activation of the Na /H exchanger 1 (NHE1). ROS formation in CD4 T cells plays a decisive role in regulating inflammatory responses. In the present study, we explored whether DJ-1 is expressed in CD4 T cells, and affects ROS production as well as NHE1 in those cells. To this end, DJ-1 and NHE1 transcript, and protein levels were quantified by qRT-PCR and Western blotting, respectively, intracellular pH (pH ) utilizing bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, NHE activity from realkalinization after an ammonium pulse, and ROS production utilizing 2',7' -dichlorofluorescin diacetate (DCFDA) fluorescence. As a result DJ-1 was expressed in CD4 T cells. ROS formation, NHE1 transcript levels, NHE1 protein, and NHE activity were higher in CD4 T cells from DJ-1 deficient mice than in CD4 T cells from wild type mice. Antioxidant N-acetyl-cysteine (NAC) and protein tyrosine kinase (PTK) inhibitor staurosporine decreased the NHE activity in DJ-1 deficient CD4 T cells, and blunted the difference between DJ-1 and DJ-1 CD4 T cells, an observation pointing to a role of ROS in the up-regulation of NHE1 in DJ-1 CD4 T cells. In conclusion, DJ-1 is a powerful regulator of ROS production as well as NHE1 expression and activity in CD4 T cells. J. Cell. Physiol. 232: 3050-3059, 2017. © 2016 Wiley Periodicals, Inc.

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“…We also demonstrated that treatment with fetuin-B increased SDF-1 expression in VSMCs and migration of monocytes and macrophages, implying activation of monocytes and macrophages by fetuin-B. Previously, we showed that SDF-1 stimulated the action of Tcells via the epigenetic regulation of C-X-C chemokine receptor type 4 (CXCR4) receptor expression [56]. Moreover, flow cytometry analysis revealed that fetuin-B increased the deposition of lipid and production of the proinflammatory cytokines, TNF-α and IL-6, in macrophages which may be involved in plaque stability [57,58].…”

Section: Discussionmentioning

confidence: 81%

The serum protein fetuin-B is involved in the development of acute myocardial infarction

et al. 2015

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The rupture of an atherosclerotic plaque is one of the main causes of coronary artery thrombotic occlusion, leading to myocardial infarction. However, the exact mechanism and causal risk factors for plaque rupture remain unclear. To identify a potential molecule that can influence atherosclerotic plaque rupture, we investigated protein expression in serum from patients with acute myocardial infarction (AMI) and stable angina (SA), using proteomic analysis. The expression of six proteins, including fibrinogen, fetuin-B, keratin 9, proapolipoprotein and fibrinogen, were altered in serum from patients with AMI compared with serum from those with SA. Of these, fetuin-B, proapolipoprotein, fibrinogen γ-B-chain precursors and fibrinogen expression were greater in serum from patients with AMI than from patients with SA. Increased fetuin-B expression in serum from AMI patients was also confirmed by Western blot analysis. Treatment with recombinant human fetuin-B increased the migration in monocytes and macrophages in a concentration-dependent manner. Fetuin-B also affected vascular plaque-stabilizing factors, including lipid deposition and cytokine production in macrophages, the activation of matrix metalloproteinase (MMP)-2 in monocytes, and the activation of apoptosis and MMP-2 in vascular smooth muscle cells. Moreover, in vivo administration of fetuin-B decreased the collagen accumulation and smooth muscle cell content and showed an increased number of macrophages in the vascular plaque. From these results, we suggest that fetuin-B may act as a modulator in the development of AMI. This study may provide a therapeutic advantage for patients at high risk of AMI.

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DJ-1 protein regulates CD3+ T cell migration via overexpression of CXCR4 receptor

Cited by 22 publications

References 41 publications

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

DJ‐1/Park7 Sensitive Na⁺/H⁺ Exchanger 1 (NHE1) in CD4⁺ T Cells

The serum protein fetuin-B is involved in the development of acute myocardial infarction

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DJ-1 protein regulates CD3+ T cell migration via overexpression of CXCR4 receptor

Cited by 22 publications

References 41 publications

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

Comparison of cell-based assays for the identification and evaluation of competitive CXCR4 inhibitors

DJ‐1/Park7 Sensitive Na+/H+ Exchanger 1 (NHE1) in CD4+ T Cells

The serum protein fetuin-B is involved in the development of acute myocardial infarction

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DJ‐1/Park7 Sensitive Na⁺/H⁺ Exchanger 1 (NHE1) in CD4⁺ T Cells