Preferential Uptake of Gamma Tocopherol by Mast Cells. Does This Uptake Affect Mast Cell Cytokine Production?.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3793-3793
Author(s):  
Omar S. Aljitawi ◽  
Mathew Fitzgerald ◽  
Min Qui ◽  
Koyamangalath Krishnan ◽  
William L. Stone ◽  
...  
Keyword(s):  
Mast Cell ◽  
Vitamin E ◽  
Mast Cells ◽  
Cytokine Production ◽  
Ppar Gamma ◽  
Alpha Tocopherol ◽  
Human Mast Cell ◽  
Peroxisome Proliferator ◽  
Gamma Tocopherol ◽  
Cell Cytokine Production

Abstract Vitamin E, the main lipid soluble antioxidant, exists in eight different forms, of which α-tocopherol and γ-tocopherol are the two major forms. Previous experiments showed vitamin E uptake by macrophages that contribute to inflammation and immunity. On the other hand, vitamin E has structural similarity to the thiazolidinedione, troglitazone, a peroxisome proliferator-activated receptor (PPAR) agonist. In previous experiments we found that troglitazone (TGZ), a PPAR gamma agonist, had a negative effect on mast cell cytokine production. We therefore wondered whether vitamin E enters human mast cells, and if so, does this modulate mast cell cytokine production? We choose (interleukin) IL-6 for its pro-inflammatory properties and because it’s known to be produced by mast cells in response to stimulants used in the experiment. In this study we try to answer these two questions. Cultured human mast cell line (HMC-1) was first incubated for 24 hrs with pharmacological concentrations of both alpha and gamma forms of vitamin E (10 μM). The mast cells were then activated with phorbol-12-myristate-13-acetate [PMA (50ng/ml)] and ionomycin (5μm) for 24 hours and cell-free supernatants collected. In additional experiments, IL-1ß (10ng/mL) was added to activate mast cells. IL-6 levels in the supernatants were determined in each well utilizing ELISA. Mast cell concentrations of alpha or gamma tocopherol were measured by high pressure liquid chromatography [HPLC] and electrochemical analysis. Mast cells pre-incubated in alpha and gamma forms of vitamin E at 10 μM did not affect mast cell IL-6 production. Mast cells, however, showed uptake of both forms of tocopherols but more pronounced uptake of the gamma form (13181.05 pmole/well of gamma compared to 8742.99 pmole/well of alpha tocopherol). We conclude that mast cells appear to store both alpha and gamma tocopherols but preferentially more gamma tocopherol. Though Vitamin E and PPAR agonists have similar structures, they did not show similar effect on mast cell cytokine production, suggesting they might have different mechanisms of action.

Reciprocal regulation of cultured human mast cell cytokine production by IL-4 and IFN-γ

2000 ◽  
Vol 106 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Hiroshi Tachimoto ◽  
Motohiro Ebisawa ◽  
Tomohide Hasegawa ◽  
Tomoko Kashiwabara ◽  
Chisei Ra ◽  
...  
Keyword(s):  
Mast Cell ◽  
Cytokine Production ◽  
Human Mast Cell ◽  
Reciprocal Regulation ◽  
Ifn Γ ◽  
Cell Cytokine Production

scholarly journals Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction

2018 ◽  
Vol 19 (12) ◽  
pp. 4092 ◽  
Author(s):  
Chen Shao ◽  
Bingjie Fu ◽  
Ning Ji ◽  
Shunli Pan ◽  
Xiaoxia Zhao ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Allergic Reaction ◽  
Nuclear Factor Kappa B ◽  
Immunoglobulin E ◽  
Mast Cell Activation ◽  
Human Mast Cell ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Nuclear Factor Kappa

Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase Cγ (PLCγ), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-κB), and mitogen-activated protein kinases/cytosolic phospholipase A2 (MAPK/cPLA2). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.

scholarly journals Divergent effects of acute and prolonged interleukin 33 exposure on mast cell IgE-mediated functions

2018 ◽  
Author(s):  
Elin Rönnberg ◽  
Avan Ghaib ◽  
Carlos Ceriol ◽  
Mattias Enoksson ◽  
Michel Arock ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Prolonged Exposure ◽  
Allergic Inflammation ◽  
Acute Effect ◽  
Receptor Expression ◽  
Human Mast Cell ◽  
Interleukin 33 ◽  
Cell Functions ◽  
Ige Mediated

AbstractBackgroundEpithelial cytokines, including IL-33 and TSLP, have attracted interest because of their roles in chronic allergic inflammation-related conditions such as asthma. Mast cells are one of the major targets of IL-33, to which they respond by secreting cytokines. Most studies performed thus far have investigated the acute effects of IL-33 on mast cells.ObjectiveThe objective of this study is to investigate how acute versus prolonged exposure of human mast cells to IL-33 and TSLP affects mediator synthesis and IgE-mediated activation.MethodsHuman lung mast cells (HLMCs), cord blood-derived mast cells (CBMCs), and the ROSA mast cell line were used for this study. Surface receptor expression and the levels of mediators were measured after treatment with IL-33 and/or TSLP.ResultsIL-33 induced the acute release of cytokines. Prolonged exposure to IL-33 increased while TSLP reduced intracellular levels of tryptase. Acute IL-33 treatment strongly potentiated IgE-mediated activation. In contrast, four days of exposure to IL-33 decreased IgE-mediated activation, an effect that was accompanied by a reduction in FcεRI expression.Conclusion & Clinical RelevanceWe show that IL-33 plays dual roles for mast cell functions. The acute effect includes cytokine release and the potentiation of IgE-mediated degranulation, whereas prolonged exposure to IL-33 reduces IgE-mediated activation. We conclude that mast cells act quickly in response to the alarmin IL-33 to initiate an acute inflammatory response, whereas extended exposure to IL-33 during prolonged inflammation reduces IgE-mediated responses. This negative feedback effect suggests the presence of a novel IL-33 mediated regulatory pathway that modulates IgE-induced human mast cell responses.

scholarly journals Resveratrol inhibits IL-33–mediated mast cell activation by targeting the MK2/3–PI3K/Akt axis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Shotaro Nakajima ◽  
Kayoko Ishimaru ◽  
Anna Kobayashi ◽  
Guannan Yu ◽  
Yuki Nakamura ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Cell Activation ◽  
Cytokine Production ◽  
Allergic Diseases ◽  
Mast Cell Activation ◽  
Akt Pathway ◽  
Mouse Lung ◽  
Mouse Bone Marrow ◽  
Interleukin 33

AbstractInterleukin-33 (IL-33)/ST2–mediated mast cell activation plays important roles in the pathophysiology of allergic diseases. Hence, pharmacologically targeting the IL-33/ST2 pathway in mast cells could help to treat such diseases. We found that resveratrol inhibits IL-33/ST2–mediated mast cell activation. Resveratrol suppressed IL-33–induced IL-6, IL-13, and TNF-α production in mouse bone marrow–derived mast cells (BMMCs), mouse fetal skin–derived mast cells, and human basophils. Resveratrol also attenuated cytokine expression induced by intranasal administration of IL-33 in mouse lung. IL-33–mediated cytokine production in mast cells requires activation of the NF-κB and MAPK p38–MAPK-activated protein kinase-2/3 (MK2/3)–PI3K/Akt pathway, and resveratrol clearly inhibited IL-33–induced activation of the MK2/3–PI3K/Akt pathway, but not the NF-κB pathway, without affecting p38 in BMMCs. Importantly, resveratrol inhibited the kinase activity of MK2, and an MK2/3 inhibitor recapitulated the suppressive effects of resveratrol. Resveratrol and an MK2/3 inhibitor also inhibited IgE-dependent degranulation and cytokine production in BMMCs, concomitant with suppression of the MK2/3–PI3K/Akt pathway. These findings indicate that resveratrol inhibits both IL-33/ST2–mediated and IgE-dependent mast cell activation principally by targeting the MK2/3–PI3K/Akt axis downstream of p38. Thus, resveratrol may have potential for the prevention and treatment of broad ranges of allergic diseases.

Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2821-2828 ◽  
Author(s):  
Tatsuya Kinoshita ◽  
Kenichi Koike ◽  
Hadija Hemed Mwamtemi ◽  
Susumu Ito ◽  
Shuichi Ishida ◽  
...  
Keyword(s):  
Mast Cell ◽  
Retinoic Acid ◽  
Mast Cells ◽  
Cord Blood ◽  
Cell Development ◽  
Negative Regulator ◽  
Human Mast Cell ◽  
Target Cells ◽  
Dependent Manner ◽  
Selective Agonist

We examined the effects of retinoids on the human mast cell development using a serum-deprived culture system. When 10-week cultured mast cells derived from CD34+ cord blood cells were used as target cells, both all-trans retinoic acid (ATRA) and 9-cis RA inhibited the progeny generation under stimulation with stem cell factor (SCF) in a dose-dependent manner (the number of progeny grown by SCF plus RA at 10−7 mol/L was one tenth of the value obtained by SCF alone). The early steps in mast cell development appear to be less sensitive to RA according to the single CD34+c-kit+ cord blood cell culture study. The optimal concentration of RAs also reduced the histamine concentration in the cultured mast cells (3.00 ± 0.47 pg per cell in SCF alone, 1.44 ± 0.18 pg per cell in SCF+ATRA, and 1.41 ± 0.10 pg per cell in SCF+9-cis RA). RT-PCR analyses showed the expression of RAR, RARβ, RXR, and RXRβ messenger ribonucleic acid (mRNA) in 10-week cultured mast cells. The addition of an RAR-selective agonist at 10−10 mol/L to 10−7 mol/L decreased the number of mast cells grown in SCF, whereas an RXR-selective agonist at up to 10−8 mol/L was inactive. Among RAR subtype selective retinoids used at 10−9 mol/L to 10−7 mol/L, only the RAR agonist was equivalent to ATRA at 10−7 mol/L in its ability to inhibit mast cell growth. Conversely, the addition of excess concentrations of a RAR antagonist profoundly counteracted the retinoid-mediated suppressive effects. These results suggest that RA inhibits SCF-dependent differentiation of human mast cell progenitors through a specific receptor.

scholarly journals Effect of Vitamin E Isoforms on Bone Metabolism in C57BL/6 J Mice Fed a High Fat Diet

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1795-1795
Author(s):  
Chen Du ◽  
Gina Tran ◽  
Victorine Imrhan ◽  
Chandan Prasad ◽  
Parakat Vijayagopal ◽  
...  
Keyword(s):  
Vitamin E ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Bone Mineral ◽  
High Fat Diet ◽  
Alpha Tocopherol ◽  
Type I ◽  
High Fat ◽  
Mineral Density ◽  
Gamma Tocopherol

Abstract Objectives The purpose of this study was to compare the effects of alpha tocopherol, gamma tocopherol, and the combination of alpha and gamma tocopherols on bone mineral density (BMD), bone mineral content (BMC), and bone metabolism in C57BL/6 J mice fed a high-fat diet. Methods A total of 75 male C57BL/6 mice were randomized to either a low fat diet (LFD) with 6% fat, a high fat diet (HFD) with 20% fat, HFD supplemented with alpha tocopherol (AT), gamma tocopherol (GT), or the combination of AT and GT. LFD and HFD were provided to corresponding groups of mice without vitamin E isoform supplements for 15 weeks to induce bone loss. At the end of the 15 weeks, AT, GT, and a combination of AT and GT were added to 3 of the HFD groups and fed for 10 weeks. LFD group and one of the HFD groups were continued on the same diet for another 10 weeks without additional supplements. All mice were euthanized at the end of the 25 weeks period. Left and right fibula bones were excised, cleaned, and scanned using the Lunar PIXImus dual-energy x-ray absorptiometry (DEXA) densitometer to assess BMD, BMC, lean tissue, and fat tissue content. Serum biomarkers of bone metabolism were evaluated post euthanization. Results HFD resulted in significantly lower fibular BMD and higher tibial bone fat content in comparison to LFD. Animals in the HFD supplemented with GT, but not AT, showed significantly reduced effect of HFD in lowering BMD. Additionally, in the group fed HFD supplemented with GT, a significantly higher concentration of alkaline phosphatase (ALP) and N-terminal propeptide of type I procollagen (PINP) were noted, compared to LFD. This may be indicative of increased bone formation resulting from GT incorporated into the HFD diet. Conclusions The findings of the study suggest that different isoforms of vitamin E affect bone density and bone metabolism differently. Within the different isoforms of vitamin E, gamma tocopherol may have protective effects in bone, especially in the situation of high fat diet induced bone loss. Further examination of the mechanistic action of vitamin E isoforms on skeletal health is warranted. Funding Sources Texas Woman's University.

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