Luteolin suppresses 5-hydroxytryptamine elevation in stimulated RBL-2H3 cells and experimental colitis mice.
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ABSTRACT:
SUBMITTER: Suga N
PROVIDER: S-EPMC8325766 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lipid rafts are highly ordered membrane microdomains enriched in cholesterol, glycosphingolipids, and certain proteins. They are involved in the regulation of cellular processes in diverse cell types, including mast cells (MCs). The MC lipid raft protein composition was assessed using qualitative mass spectrometric characterization of the proteome from detergent-resistant membrane fractions from RBL-2H3 MCs. Using two different post-isolation treatment methods, a total of 949 lipid raft associated proteins were identified. The majority of these MC lipid raft proteins had already been described in the RaftProtV2 database and are among highest cited/experimentally validated lipid raft proteins. Additionally, more than half of the identified proteins had lipid modifications and/or transmembrane domains. Classification of identified proteins into functional categories showed that the proteins were associated with cellular membrane compartments, and with some biological and molecular functions, such as regulation, localization, binding, catalytic activity, and response to stimulus. Furthermore, functional enrichment analysis demonstrated an intimate involvement of identified proteins with various aspects of MC biological processes, especially those related to regulated secretion, organization/stabilization of macromolecules complexes, and signal transduction. This study represents the first comprehensive proteomic profile of MC lipid rafts and provides additional information to elucidate immunoregulatory functions coordinated by raft proteins in MCs.
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Project description:Mast cells are connective tissue resident cells with morphological and functional characteristics that contribute to their role in allergic and inflammatory processes, host defense and maintenance of tissue homeostasis. Mast cell activation results in the release of pro-inflammatory mediators which are largely responsible for the physiological functions of mast cells. The lectin ArtinM, extracted from Artocarpus heterophyllus (jackfruit), binds to D-manose, thus inducing degranulation of mast cells. ArtinM has several immunomodulatory properties including acceleration of wound healing, and induction of cytokine release. The aim of the present study was to investigate the role of ArtinM in the activation and proliferation of mast cells. The rat mast cell line RBL-2H3 was used throughout this study. At a low concentration (0.25?g/mL), ArtinM induced mast cell activation and the release of IL-6 without stimulating the release of pre-formed or newly formed mediators. Additionally, when the cells were activated by ArtinM protein tyrosine phosphorylation was stimulated. The low concentration of ArtinM also activated the transcription factor NFkB, but not NFAT. ArtinM also affected the cell cycle and stimulated cell proliferation. Therefore, ArtinM may have therapeutic applications by modulating immune responses due to its ability to activate mast cells and promote the release of newly synthesized mediators. Additionally, ArtinM could have beneficial effects at low concentrations without degranulating mast cells and inducing allergic reactions.
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Project description:Phospholipase D (PLD) hydrolyses phosphatidylcholine to produce phosphatidic acid (PA) and choline. It has two isoforms, PLD1 and PLD2, which are differentially expressed depending on the cell type. In mast cells it plays an important role in signal transduction. The aim of the present study was to clarify the role of PLD2 in the secretory pathway. RBL-2H3 cells, a mast cell line, transfected to overexpress catalytically active (PLD2CA) and inactive (PLD2CI) forms of PLD2 were used. Previous observations showed that the Golgi complex was well organized in CA cells, but was disorganized and dispersed in CI cells. Furthermore, in CI cells, the microtubule organizing center was difficult to identify and the microtubules were disorganized. These previous observations demonstrated that PLD2 is important for maintaining the morphology and organization of the Golgi complex. To further understand the role of PLD2 in secretory and vesicular trafficking, the role of PLD2 in the secretory process was investigated. Incorporation of sialic acid was used to follow the synthesis and transport of glycoconjugates in the cell lines. The modified sialic acid was subsequently detected by labeling with a fluorophore or biotin to visualize the localization of the molecule after a pulse-chase for various times. Glycoconjugate trafficking was slower in the CI cells and labeled glycans took longer to reach the plasma membrane. Furthermore, in CI cells sialic acid glycans remained at the plasma membrane for longer periods of time compared to RBL-2H3 cells. These results suggest that PLD2 activity plays an important role in regulating glycoconjugate trafficking in mast cells.
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Project description:In patients with chronic pulmonary disease colonization with the mold Aspergillus fumigatus is associated with declining pulmonary function and obstructive airway disease. One potential effector of this inflammatory response is the pulmonary mast cell. In vitro studies have demonstrated that A. fumigatus contact induces IgE-independent mast cell degranulation. Conversely, the Aspergillus secondary metabolite gliotoxin has been shown to suppress mast cell activation. These contradictory results emphasize the need for a better understanding of the interactions between A. fumigatus and mast cells. Thus, the objective of this work was to identify A. fumigatus genes that are differentially regulated upon exposure to mast cells. Transcriptional profiling experiments indicated that, in addition to genes encoding for iron acquisition systems, allergens and putative virulence factors, genes from the gliotoxin biosynthesis cluster were significantly down-regulated upon exposure to mast cells. Globally, the results from this study provide insight into the A. fumigatus response to mast cells and suggest that one mechanism by which the host may circumvent the effects of gliotoxin is via the suppression of fungal gliotoxin synthesis by mast cells.
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Project description:In a previous study, we demonstrated the anti-inflammatory activity of the essential oil extracted from Korean pine (Pinus koraiensis, Sieb. et Zucc.) wood. This study aims to investigate the active anti-inflammatory constituents of P. koraiensis oil. The essential oil was extracted from P. koraiensis wood by hydrodistillation and was divided into six fractions (A-F) through fractional distillation. Then, the anti-inflammatory activities of the fractions (A-F) were determined. Fractions A and F markedly downregulated the production of pro-inflammatory cytokines as well as the secretion of β-hexosaminidase in lipopolysaccharide (LPS)-stimulated RBL-2H3 cells. The main constituents of the active anti-inflammatory A and F fractions were (+)-α-pinene, (-)-β-pinene, (+)-α-terpineol, 3-carene, (+)-limonene, and longifolene. These six single compounds decreased the expression of inflammatory-related genes (i.e., IL-4 and IL-13) as well as the secretion of β-hexosaminidase in LPS-stimulated RBL-2H3 cells. (+)-α-Pinene, (-)-β-pinene, (+)-α-terpineol, and longifolene exhibited the strongest effects; these effects were comparable to those of the positive control (i.e., dexamethasone). The findings indicate that the interactions between these components exhibit potential for the management and/or treatment of inflammatory conditions as well as base structures for the development of novel anti-inflammatory drugs.
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Project description:Mast cells (MCs) are inflammatory cells involved in allergic reactions. Crosslinking of the high-affinity receptor for IgE (FcϵRI) with multivalent antigens (Ags) induces secretory responses to release various inflammatory mediators. These responses are largely mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Vesicle-associated membrane protein 3 (VAMP3) is a vesicular-SNARE that interacts with targeted SNARE counterparts, driving the fusion of MC secretory granules with the membrane and affecting subsequent assembly of the plasma membrane. However, the role of VAMP3 in FcϵRI-mediated MC function remains unclear. In this study, we comprehensively examined the role of VAMP3 and the molecular mechanisms underlying VAMP3-mediated MC function upon FcϵRI activation. VAMP3 shRNA transduction considerably decreased VAMP3 expression compared with non-target shRNA-transduced (NT) cells. VAMP3 knockdown (KD) cells were sensitized with an anti-DNP IgE antibody and subsequently stimulated with Ag. The VAMP3 KD cells showed decreased degranulation response upon Ag stimulation. Next, we observed intracellular granule formation using CD63-GFP fluorescence. The VAMP3 KD cells were considerably impaired in their capacity to increase the size of granules when compared to NT cells, suggesting that VAMP3 mediates granule fusion and therefore promotes granule exocytosis in MCs. Analysis of FcϵRI-mediated activation of signaling events (FcϵRI, Lyn, Syk, and intracellular Ca2+ response) revealed that signaling molecule activation was enhanced in VAMP3 KD cells. We also found that FcϵRI expression on the cell surface decreased considerably in VAMP3 KD cells, although the amount of total protein did not vary. VAMP3 KD cells also showed dysregulation of plasma membrane homeostasis, such as endocytosis and lipid raft formation. The difference in the plasma membrane environment in VAMP3 KD cells might affect FcϵRI membrane dynamics and the subsequent signalosome formation. Furthermore, IgE/Ag-mediated secretion of TNF-α and IL-6 is oppositely regulated in the absence of VAMP3, which appears to be attributed to both the activation of FcϵRI and defects in VAMP3-mediated membrane fusion. Taken together, these results suggest that enhanced FcϵRI-mediated signal transduction in VAMP3 KD cells occurs due to the disruption of plasma membrane homeostasis. Hence, a multifunctional regulation of VAMP3 is involved in complex secretory responses in MCs.
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Project description:For the first time we show the effects of deuterium oxide on cell growth and vesicle transport in rat basophilic leukemia (RBL-2H3) cells. RBL-2H3 cells cultured with 15 moles/L deuterium showed decreased cell growth which was attributed to cells not doubling their DNA content. Experimental observations also showed an increase in vesicle speed for cells cultured in deuterium oxide. This increase in vesicle speed was not observed in deuterium oxide cultures treated with a microtubule-destabilizing drug, suggesting that deuterium oxide affects microtubule-dependent vesicle transport.
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Project description:Treatments of inflammatory bowel disease (IBD) are diverse, but their efficacy is limited, and it is therefore urgent to find better therapies. Controlling mucosal inflammation is a must in IBD drug treatment. The occurrence of anti-tumor necrosis factor α (TNF-α) monoclonal antibodies has provided a safer and more efficacious therapy. However, this kind of treatment still faces failure in the form of loss of response. β-Carboline alkaloids own an anti-inflammatory pharmacological activity. While Kumujan B contains β-carboline, its biological activity remains unknown. In this study, we attempted to determine the anti-inflammatory effects of Kumujan B using both the TNF-α- induced in vitro inflammation and DSS-induced in vivo murine IBD models. Our data show that Kumujan B attenuated the expression of interleukin 1β (IL-1β) and interleukin 6 (IL-6) induced by TNF-α in mouse peritoneal macrophages. Kumujan B suppressed c-Jun N-terminal protein kinases (JNK) signaling, especially c-Jun, for anti-inflammatory response. Furthermore, Kumujan B promoted K11-linked ubiquitination and degradation of c-Jun through the proteasome pathway. In an in vivo study, Kumujan B inhibited the expression of IL-1β, IL-6, and TNF-α and improved the colon barrier function in dextran sulfate sodium salt (DSS)-induced experimental mice colitis. Kumujan B exhibited in vivo and in vitro anti-inflammatory effects, making it a potential therapeutic candidate for treating IBD.
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Project description:Objective and designTo determine whether the neurokinin-1 receptor (NK1R) plays a role in the activation of RBL-2H3 mast cells after Fc?R? aggregation.Materials and methodsNK1R expression in RBL-2H3 cells was inhibited by small hairpin RNA (shRNA) against NK1R, and determined by western blotting. For activation, both NK1R knockdown and control RBL-2H3 cells were sensitized by dinitrophenol (DNP)-specific IgE and stimulated with the antigen DNP-bovine serum albumin (BSA). Following the activation of RBL-2H3 cells, monocyte chemoattractant protein (MCP-1) production and intracellular calcium flux were monitored by ELISA and confocal microscopy assay, respectively. For investigation of the signaling mechanism, phosphorylation of mitogen-activated protein kinases (MAPKs) after RBL-2H3 cell activation was assessed by western blotting.ResultsshRNA-NK1R mediated an effective inhibition of NK1R expression in RBL-2H3 cells. Protein production of MCP-1 was reduced by more than 55 % in NK1R knockdown RBL-2H3 cells compared with control RBL-2H3 cells. In addition, both calcium mobilization and phosphorylation levels of MAPKs (Erk1/2, JNK, and p38) after DNP-BSA stimulation (via Fc?R?) were decreased due to the inhibition of NK1R expression.ConclusionNK1R is required for the activation of RBL-2H3 cells following Fc?R? engagement and involved in the regulation of MAPK signaling pathways.
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Project description:Cuminum cyminum L. (cumin) seed is used as a spice in various countries. Although several functions of the components in cumin seed have been reported, the anti-allergic effect of the water-soluble component in cumin seed has not been reported yet. In this study, we focused on the suppressive effect of cumin seed aqueous extract on degranulation in order to reveal the anti-allergic effect of cumin. Cumin seed aqueous extract significantly suppressed the antigen-induced degranulation of rat basophilic leukemia cell line RBL-2H3 cells in a dose-dependent manner without cytotoxicity. The extract also inhibited the elevation of the intracellular calcium ion concentration induced by antigen. Immunoblot analysis revealed that the extract suppresses phosphorylation of phosphatidylinositol 3-kinase, Bruton's tyrosine kinase, phospholipase C-γ1/2, and Akt in the signaling pathways activated by antigen induction via FcεRI. Furthermore, the extract suppressed microtubule formation induced by antigen. In addition, oral administration of cumin seed aqueous extract significantly suppressed the passive cutaneous anaphylaxis reaction in BALB/c mice. Our findings suggest that cumin seed contains water-soluble components with the anti-allergic effect. Therefore, cumin seed has potential as anti-allergic functional food.
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