Cell-permeable ceramides act as novel regulators of U937 cell–cell adhesion mediated by CD29, CD98, and CD147

Mediators of Inflammation

et al. 2014

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21-O-Angeloyltheasapogenol E3 (ATS-E3) is a triterpenoid saponin recently isolated from the seeds of the tea tree Camellia sinensis (L.) O. Kuntze. ATS-E3 has several beneficial properties including anti-inflammatory, antidiabetic, antiatherosclerotic, and anticancer effects. Unlike other phenolic compounds isolated from tea plants, there are no studies reporting the pharmacological action of ATS-E3. In this study, we therefore aimed to explore the cellular and molecular inhibitory activities of ATS-E3 in macrophage-mediated inflammatory responses. ATS-E3 remarkably diminished cellular responses of macrophages such as FITC-dextran-induced phagocytic uptake, sodium nitroprusside- (SNP-) induced radical generation, and LPS-induced nitric oxide (NO) production. Analysis of its molecular activity showed that this compound significantly suppressed the expression of inducible NO synthase (iNOS), nuclear translocation of nuclear factor- (NF-) κB subunits (p50 and p65), phosphorylation of inhibitor of κB kinase (IKK), and the enzyme activity of AKT1. Taken together, the novel triterpenoid saponin compound ATS-E3 contributes to the beneficial effects of tea plants by exerting anti-inflammatory and antioxidative activities in an AKT/IKK/NF-κB-dependent manner.

Section: Methodsmentioning

confidence: 99%

21-O-Angeloyltheasapogenol E3, a Novel Triterpenoid Saponin from the Seeds of Tea Plants, Inhibits Macrophage-Mediated Inflammatory Responses in a NF-κB-Dependent Manner

Yang

Mediators of Inflammation

et al. 2014

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“…In innate immunity, macrophages and monocytes are representative cells governing various cellular functions such as cell adhesion to target cells or to tissues via functional activation of cell adhesion molecules [e.g., cluster of differentiation (CD) 29 (CD29), CD43, and CD44]; cell migration to infected sites; phagocytic uptake of infected pathogens; release of cytotoxic radical molecules [e.g., reactive oxygen/nitrogen species (ROS/RNS)]; the production of proinflammatory cytokines/mediators [e.g., tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, prostaglandin E 2 , and nitric oxide]; and the stimulation of other adaptive immune cells through the expression of costimulatory molecules (e.g., CD69, CD80, and CD86) by mediating redox-sensitive transcription factors such as nuclear factor-kappa-B (NF-κB) and activator protein 1 (AP-1) [4], [5], [7], [8]. Therefore, macrophages and monocytes have critical roles in antibacterial, antiviral, and antifungal responses in innate immunity [1], [2], [3], [4], [5], [9], [10], [11].…”

Section: Introductionmentioning

confidence: 99%

Nuclear factor kappa-B- and activator protein-1-mediated immunostimulatory activity of compound K in monocytes and macrophages

Yang

Journal of Ginseng Research

et al. 2017

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BackgroundCompound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses.MethodsThe immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes.ResultsCompound K induced cell cluster formation through cell-cell adhesion, cell migration, and phagocytic activity, but it suppressed cell-tissue interactions in U937 and RAW264.7 cells. Compound K also upregulated the surface expression of the cell adhesion molecule cluster of differentiation (CD) 43 (CD43) and costimulatory molecules CD69, CD80, and CD86, but it downregulated the expression of monocyte differentiation marker CD82 in RAW264.7 cells. Moreover, CK induced the release of reactive oxygen species and induced messenger RNA expression of proinflammatory genes, inducible nitric oxide synthase, and tumor necrosis factor-alpha by enhancing the nuclear translocation and transcriptional activities of nuclear factor kappa-B and activator protein-1.ConclusionOur results suggest that CK has an immunomodulatory role in innate immune responses through regulating various cellular events mediated by monocytes and macrophages.

“…These findings have raised the possibility that functional regulation of CD29 by small molecules or therapeutic antibodies could become a useful therapeutic strategy in treating autoimmune and chronic inflammatory diseases. We have reported that lancemaside A, 20S-dihydroprotopanaxadiol, cinnamaldehyde, ceramide, chloroquine, and cynaropicrin are regarded as good modulators of CD29-mediated cell-cell adhesion [254647]. Others have found that ibrutinib (an orally active covalent BTK inhibitor) [48], shikonin [49], and biodentine [50] can inhibit the functional activation of integrins.…”

Section: Discussionmentioning

confidence: 99%

“…Images of cells in culture were observed using an inverted phase-contrast microscope attached to a video camera, and captured using NIH image software as reported previously [25]. …”

Section: Methodsmentioning

confidence: 99%

Molecular association of CD98, CD29, and CD147 critically mediates monocytic U937 cell adhesion

Korean J Physiol Pharmacol

Cho

2016

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Adhesion events of monocytes represent an important step in inflammatory responses induced by chemokines. The β1-integrin CD29 is a major adhesion molecule regulating leukocyte migration and extravasation. Although several adhesion molecules have been known as regulators of CD29, the molecular interactions between CD29 and its regulatory adhesion molecules (such as CD98 and CD147) have not been fully elucidated. Therefore, in this study, we examined whether these molecules are functionally, biochemically, and cell-biologically associated using monocytic U937 cells treated with aggregation-stimulating and blocking antibodies, as well as enzyme inhibitors. The surface levels of CD29, CD98, and CD147 (but not CD43, CD44, and CD82) were increased. The activation of CD29, CD98, and CD147 by ligation of them with aggregation-activating antibodies triggered the induction of cell-cell adhesion, and sensitivity to various enzyme inhibitors and aggregation-blocking antibodies was similar for CD29-, CD98-, and CD147-induced U937 cell aggregation. Molecular association between these molecules and the actin cytoskeleton was confirmed by confocal microscopy and immunoprecipitation. These results strongly suggest that CD29 might be modulated by its biochemical and cellular regulators, including CD98 and CD147, via the actin cytoskeleton.