Blockage of Wnt/β-catenin signaling by quercetin reduces survival and proliferation of B-1 cells in vitro

Novo, Marilia Campos Tavares; Osugui, Lika; Reis, Vanessa O.; Longo-Maugéri, Ieda Maria; Mariano, Mário; Popi, Ana Flávia

doi:10.1016/j.imbio.2014.09.001

Cited by 34 publications

(28 citation statements)

References 43 publications

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“…It is well-known that PI3K/AKT signaling plays acritical role in modulating cell survival and apoptosis [34], and it have been found overactivated in many cancers reducing apoptosis and promoting proliferation [35]. Wnt/β-catenin signaling pathway is important for cell proliferation and differentiation [36]. The activation of PI3K/AKT can activate the Wnt signaling through the phosphorylation of GSK-3β by the phosphorylated Akt1/2, blocking the formation of β-catenin destroying complies [37].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes

Sun

Song

et al. 2017

Cell Physiol Biochem

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Key WordsInflammatory injury • MicroRNA-146a • C-X-C chemokine receptor type 4 • PI3K/AKT • Wnt/β-catenin Abstract Background/Aims: Osteoarthritis (OA) as a degenerative disease is a major problem in ageing populations. To better understand the molecular mechanisms in the pathogenesis of OA, this study explored the role of microRNA (miR)-146a in the articular chondrocytes. Methods: The articular chondrocyte line ATDC5 was used to simulate inflammatory injury by LPS administration in vitro. Cell viability, apoptosis, mRNA expressions and productions of inflammatory factors were assessed, respectively. Mir-146a and Cxcr4 mRNA expressions were measured by qRT-PCR. Targeting effect of miR-146a on Cxcr4 3'UTR was assessed by luciferase activity analysis. Protein expression levels of CXCR4 and main factors in PI3K/AKT, Wnt/β-catenin signal pathways were measured by western blotting. Results: LPS exposure suppressed cell viability, prompted apoptosis of ATDC5 cells, and stimulated expression and release of inflammatory factors. MiR-146a was upregulated in LPS-induced cells. Overexpression of miR146a further aggravated LPS-induced inflammatory injury, while it was reduced after miR146a was knocked down. CXCR4 expression was negatively regulated by miR-146a. CXCR4 was a direct target of miR-146a and thus involved in regulatory effect of miR-146a on the injured chondrocytes, which was also related with phosphorylation levels of PI3K/AKT and expressions of Wnt/β-catenin signal factors. Conclusion: miR-146a promoted inflammatory response of articular chondrocytes via targeting CXCR4 and suppressing CXCR4 expression. Overexpression of CXCR4 could attenuate the inflammatory injury. Our findings provided novel evidence which might be useful for further studies exploring therapeutic approaches for OA via targeting miR-146a.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes

Sun

Song

et al. 2017

Cell Physiol Biochem

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“…Several reports demonstrate that exposure to Wnts can condition dendritic cells (DCs) to a regulatory state, while β-catenin in DCs drives T regulatory cell differentiation via the Toll-like receptor 2 and plays a critical role in tolerance and autoimmune disorders [15–17]. The Wnt pathway also regulates CD4+/CD8+ differentiation and B cell development [18–20]. …”

Section: Discussionmentioning

confidence: 99%

Impairment of Wnt/β-catenin signaling in blood cells of patients with severe cavitary pulmonary tuberculosis

et al. 2017

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Tuberculosis (TB) remains as a leading infectious disease worldwide. Our previous study showed interferon (IFN)-γ and CD3 T cell impairment in patients with severe cavitary pulmonary TB (PTB). However, the cause of the change in immune responses during the progression of TB is still poorly understood. In this study, eight newly diagnosed patients with severe cavitary and mild lesion non-cavity PTB were recruited, and three healthy volunteers were recruited as the control. RNA extracted from blood was tested by whole genome oligo microarrays. A PCR array was used to further test the same samples. Two additional groups of patients were recruited according to the same criteria with healthy control(HC) recruited as well and subjected to peripheral blood mononuclear cell isolation (PBMC)and analysis of TCF-7, β-catenin, cyclin D2, IFN-γ, and tumor necrosis factor (TNF)-α expression in CD14- cells (lymphocytes) and CD14+ cells by quantitative PCR. The changes of expression of β-catenin, CD69+ and IFN-γ by CD3+, CD14- and CD14+ cells in vitro with stimulation of LiCl were tested by flow cytometry. Whole genome oligo microarrays showed a significant decrease in expression of the Wnt signaling pathway in severe PTB patients. Further analysis of the Wnt pathway by PCR array indicated that TCF-7, β-catenin, and cyclin D2 expression was significantly reduced in severe PTB patients compared with mild PTB patients. In the additionally recruited patients, TCF-7, β-catenin, and cyclin D2 were expressed in both CD14+ and CD14- cells, while β-catenin was decreased significantly in CD14- cells compared with CD14+ cells in severe PTB patients, and IFN-γ and TNF-α expression in CD14- cells was also reduced significantly in severe PTB patients. β-catenin can directly trigger T cell activation and IFN-γsecretion in PBMCs stimulated for 24 hours. These findings indicate that Wnt pathway and its key genes, such as β-catenin, were impaired in blood cells of patients with severe PTB. Therefore, Wnt/β-catenin pathway is closely associated with T cell proliferation and TB lesion deterioration.

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“…Interestingly, a constitutive activation of STAT3 is found in normal self-renewing B1 cells (75). On the other hand, the Wnt/bcatenin pathway is involved in the regulation of proliferation and survival of B1 cells and also promotes self-renewal of these cells (76). Altogether, overactivation of these two pathways may explain the increased number of different B cell subsets observed in HOCl-animals and the abrogation of immune B cell abnormalities mediated through their inhibition upon treatment with niclosamide in HOCl-mice.…”

Section: Discussionmentioning

confidence: 99%

Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species–Induced Mouse Model

Morin

Kavian

Nicco

et al. 2016

The Journal of Immunology

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Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy, and immunological abnormalities. Recent insights on the implication of STAT3, AKT, and Wnt/β-catenin in fibrosis have prompted us to investigate, in a mouse model of ROS-induced SSc, the effects of niclosamide, an antihelmintic drug that inhibits both of these signaling pathways. SSc was induced in BALB/c mice by daily s.c. injections of hypochlorous acid (HOCl). Mice were treated or not every other day, 5 d a week, for 6 wk, by niclosamide. Skin and lung fibrosis as well as immunological features were studied. Mice exposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase 1 autoantibodies. STAT3, AKT, and Wnt/β-catenin pathways were hyperactivated in the skin and the lungs of diseased mice. Niclosamide reversed fibrosis of the skin and the lungs. Beneficial immunological effects were also observed because niclosamide decreased the activation of CD4+ and CD8+ T cells, autoimmune B cell activation, as well as IL-4 and IL-13 production in the skin. The improvement permitted by niclosamide in the mouse model of HOCl-induced SSc as well as the well-documented safety profile of this drug provide a rationale for the evaluation of niclosamide in the management of patients affected by this disease.

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Blockage of Wnt/β-catenin signaling by quercetin reduces survival and proliferation of B-1 cells in vitro

Cited by 34 publications

References 43 publications

MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes

MiR-146a Aggravates LPS-Induced Inflammatory Injury by Targeting CXCR4 in the Articular Chondrocytes

Impairment of Wnt/β-catenin signaling in blood cells of patients with severe cavitary pulmonary tuberculosis

Niclosamide Prevents Systemic Sclerosis in a Reactive Oxygen Species–Induced Mouse Model

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