Serum inhibitors for human mast cell growth: possible role of retinol

Ishida, Shuichi; Kinoshita, Tatsuya; Sugawara, Naoto; Yamashita, Tetsuji; Koike, Kenichi

doi:10.1034/j.1398-9995.2003.00270.x

Cited by 25 publications

(10 citation statements)

References 25 publications

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“…Indeed, we found that OKT-3/IL-2-induced T cell proliferation was very sensitive to RA, responding to RA concentrations as low as 10 pmol. Moreover, the FBS that was used in the present study contained ϳ0.6 M retinol (data not shown), a concentration that is comparable to that found by others (33,34). Accordingly, when studying the effects of RA or retinol on T cells, serum has frequently been omitted from the culture medium (52)(53)(54).…”

Section: Discussionmentioning

confidence: 69%

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All-transRetinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3

Engedal

Gjevik

Blomhoff

et al. 2006

The Journal of Immunology

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Vitamin A is established as an important immune regulator, but the mechanisms whereby vitamin A regulates T cell biology are poorly defined. In this study, we show that an active metabolite of vitamin A, all-trans retinoic acid (RA), potently stimulates T cell proliferation by modulating IL-2-mediated signaling downstream of IL-2R and independent of the induction of IL-2. Thus, at concentrations as low as 0.1 nM, RA enhanced the division of normal human T lymphocytes that were simultaneously stimulated with anti-CD3 mAbs and saturating concentrations of IL-2. At the optimal concentration of RA (50 nM), a 3-fold increase in T cell proliferation was observed. The induced proliferation was preceded by increased phosphorylation of the retinoblastoma protein and enhanced G1- to S-phase progression. Interestingly, the promitogenic effect of RA was found to be particularly directed toward increased expression of cyclin D3 at both the mRNA and protein level. Furthermore, the stimulatory effect of RA on cyclin D3 expression as well as on cell proliferation was completely abolished in the presence of the JAK inhibitor AG-490 or blocking IL-2Rα mAbs, and RA also enhanced cyclin D3 expression and T cell proliferation in the presence of IL-2 alone. Finally, we showed that the proliferative effect of RA was mimicked by agonists of the retinoic acid receptor (RAR) and completely inhibited by a RAR-selective antagonist. In conclusion, our results indicate that RA, via RAR, stimulates IL-2-induced signaling in a JAK-dependent manner to enhance cyclin D3 expression and thereby promote T cell proliferation.

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Section: Discussionmentioning

confidence: 69%

“…1A). FBS is known to contain the parent vitamin A compound retinol (33,34), which may be intracellularly metabolized to RA and thereby mask the effect of exogenously added RA. The retinol content in a given batch of FBS will vary depending on, for example, conditions of storage and handling.…”

Section: Ra Potentiates T Cell Proliferation Induced By Okt-3 and Il-2mentioning

confidence: 99%

All-transRetinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3

Engedal

Gjevik

Blomhoff

et al. 2006

The Journal of Immunology

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“…However, previous reports provide evidence that serum-free conditions allow for more efficient development of human MCs than do serum-containing conditions [31,32]. Thus, to minimize potentially suppressing or even inhibiting effects of serum on MC development [49], serum-free culture conditions were selected for the present protocol. Regarding the various cytokines and their concentrations used in this protocol, the following points merit comment.…”

Section: Discussionmentioning

confidence: 99%

A protocol for generating high numbers of mature and functional human mast cells from peripheral blood

Lappalainen

Lindstedt

Kovanen

2007

Clin Experimental Allergy

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“…This is in line with previous observations. Retinol and RA were shown to inhibit the growth and differentiation of human leukemic mast cells (HMC-1) (102), and the mast cells derived from peripheral blood or cord blood samples (103,104). Peritoneal mast cell numbers were also reported to be 1.5 times higher in VAD rat (105).…”

Section: Regulation Of Mmp9 (In Macrophage Dcs and Intestinal Epithementioning

confidence: 99%

RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes

Chai¹,

Lyu²,

Chen³

et al. 2019

Preprint

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Vitamin A (VA) deficiency remains prevalent in resource limited countries, affecting over 250 million preschool aged children. Vitamin A deficiency is associated with reduced 2 intestinal barrier function and increased risk of mortality due to mucosal infection. Citrobacter rodentium (C. rodentium) infection in mice is a model for diarrheal diseases in humans. During C. rodentium infection, vitamin A deficient (VAD) mice displayed reduced survival rate and pathogen clearance compared to their vitamin A sufficient (VAS) counterparts. Objectives: To characterize and compare the impact of vitamin A (VA) deficiency on gene expression patterns in the small intestine (SI) and the colon, and to discover novel target genes in VA-related biological pathways. Methods: vitamin A deficient (VAD) mice were generated by feeding VAD diet to pregnant C57/BL6 dams and their post-weaning offspring. Total mRNA extracted from SI and colon were sequenced using Illumina HiSeq 2500 platform. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to characterize expression patterns and co-expression patterns. Results:The comparison between VAS and VAD groups detected 49 and 94 DEGs in SI and colon, respectively. According to GO information, DEGs in the SI demonstrated significant enrichment in categories relevant to retinoid metabolic process, molecule binding, and immune function. Immunity related pathways, such as "humoral immune response" and "complement activation," were positively associated with VA in SI. On the contrary, in colon, "cell division" was the only enriched category and was negatively associated with VA. Three co-expression modules showed significant correlation with VA status in SI and were identified as modules of interest. Those modules contained four known retinoic acid targets. Therefore we have prioritized the other module members (e.g. Mbl2, Mmp9, Cxcl14, and Nr0b2) to be investigated as candidate genes regulated by VA. Also in SI, markers of two cell types, Mast cell and Tuft cell, were found altered by VA status. Comparison of co-expression modules between SI and colon indicated distinct regulatory networks in these two organs. Material and MethodsAnimals. C57BL/6 mice, originally purchased from Jackson Laboratories (Bar Harbor, MN), were bred and maintained at the Pennsylvania State University (University Park, PA) for experiments. Mice were exposed to a 12 hour light, 12 hour dark cycle with ad libitum access to food and water. All animal experiments were performed according to the Pennsylvania State University's Institutional Animal Care and Use Committee (IACUC) guideline (IACUC # 43445). Vitamin A deficient (VAD) and vitamin A sufficient (VAS) mice were generated as previously described (23,(27)(28)(29). Briefly, VAS or VAD diets were fed to pregnant mothers and the weanlings. VAS diet contained 25 μg of retinyl acetate per day whereas VAD diet did not contain any VA. At weaning, mice were maintained on their respective d...

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Serum inhibitors for human mast cell growth: possible role of retinol

Abstract: Our results suggest that retinol and its derivatives act as a circulating regulator for human mast cell growth. The RARalpha antagonist may be a useful tool to obtain higher numbers of mast cells in FBS-containing cultures.

Cited by 25 publications

References 25 publications

All-transRetinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3

All-transRetinoic Acid Stimulates IL-2-Mediated Proliferation of Human T Lymphocytes: Early Induction of Cyclin D3

A protocol for generating high numbers of mature and functional human mast cells from peripheral blood

RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, uncovering novel vitamin A-regulated genes

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