scholarly journals All-trans-Retinoic Acid Imprints Expression of the Gut-Homing Marker α4β7 while Suppressing Lymph Node Homing of Dendritic Cells

2013 ◽  
Vol 20 (10) ◽  
pp. 1642-1646 ◽  
Author(s):  
Tristan I. Evans ◽  
R. Keith Reeves
Keyword(s):  
Dendritic Cells ◽  
Retinoic Acid ◽  
Lymph Node ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Atra Treatment ◽  
Lymph Node Homing ◽  
All Trans Retinoic Acid ◽  
Trafficking Receptor ◽  
Dose Dependent

ABSTRACTTissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or direct vaccine carriers is highly attractive for the next generation of vaccines and immunotherapeutics. Since these types of studies would undoubtedly be first conducted using nonhuman primate models, we evaluated the ability of all-trans-retinoic acid (ATRA) to induce gut-homing α4β7 expression on rhesus macaque plasmacytoid and myeloid DCs (pDCs and mDCs, respectively). Induction of α4β7 occurred in both a time-dependent and a dose-dependent manner with up to 8-fold increases for mDCs and 2-fold increases for pDCs compared to medium controls. ATRA treatment was also specific in inducing α4β7 expression, but not expression of another mucosal trafficking receptor, CCR9. Unexpectedly, upregulation of α4β7 was associated with a concomitant downregulation of CD62L, a marker of lymph node homing, indicating an overall shift in the trafficking repertoire. These same phenomena occurred with ATRA treatment of human and chimpanzee DCs, suggesting a conserved mechanism among primates. Collectively, these data serve as a first evaluation forex vivomodification of primate DC homing patterns that could later be used in reinfusion studies for the purposes of immunotherapeutics or mucosa-directed vaccines.

scholarly journals All-Trans Retinoic Acid Enhances Bacterial Flagellin-Stimulated Proinflammatory Responses in Human Monocyte THP-1 Cells by Upregulating CD14

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Thi Xoan Hoang ◽  
Jong Hyeok Jung ◽  
Jae Young Kim
Keyword(s):  
Retinoic Acid ◽  
Cell Surface ◽  
Human Monocyte ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Dependent Manner ◽  
Atra Treatment ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Proinflammatory Responses

All-trans retinoic acid (ATRA), an active form of vitamin A, exerts immunomodulatory functions. In this study, we examined the immune potentiating effect of ATRA on bacterial flagellin-induced NF-κB activation and proinflammatory cytokine production in human monocytic cell line THP-1. ATRA treatment significantly enhanced the flagellin-induced NF-κB/AP-1 activity in THP-1 via the RAR/RXR pathway. Similarly, ATRA enhanced the expression and production of TNF-α and IL-1β in THP-1 cells upon flagellin challenge. The cell surface expression of toll-like receptor 5 (TLR5), which is the receptor for bacterial flagellin, was significantly reduced by ATRA in a concentration- and time-dependent manner. To determine the mechanisms underlying the ATRA-enhanced immune response against bacterial flagellin despite the reduced cell surface expression of TLR5 in ATRA-treated THP-1, we examined the cell surface expression of CD14, which has been proposed to be a TLR co-receptor that enhances the response to microbial components. The cell surface expression of CD14 was significantly enhanced by ATRA treatment, especially in the presence of flagellin. Anti-CD14 antibody treatment prior to ATRA and flagellin treatments completely abolished ATRA-enhanced TNF-α and IL-1β production. Our results suggest that ATRA enhances flagellin-stimulated proinflammatory responses in human monocyte THP-1 cells by upregulating CD14 in a RAR/RXR-dependent manner.

scholarly journals Excessive All-Trans Retinoic Acid Inhibits Cell Proliferation Through Upregulated MicroRNA-4680-3p in Cultured Human Palate Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Hiroki Yoshioka ◽  
Sai Shankar Ramakrishnan ◽  
Junbo Shim ◽  
Akiko Suzuki ◽  
Junichi Iwata
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Cleft Palate ◽  
Specific Inhibitor ◽  
Dependent Manner ◽  
Altered Expression ◽  
Expression Of Genes ◽  
All Trans Retinoic Acid ◽  
Congenital Birth Defect ◽  
Dose Dependent

Cleft palate is the second most common congenital birth defect, and both environmental and genetic factors are involved in the etiology of the disease. However, it remains largely unknown how environmental factors affect palate development. Our previous studies show that several microRNAs (miRs) suppress the expression of genes involved in cleft palate. Here we show that miR-4680-3p plays a crucial role in cleft palate pathogenesis. We found that all-trans retinoic acid (atRA) specifically induces miR-4680-3p in cultured human embryonic palatal mesenchymal (HEPM) cells. Overexpression of miR-4680-3p inhibited cell proliferation in a dose-dependent manner through the suppression of expression of ERBB2 and JADE1, which are known cleft palate-related genes. Importantly, a miR-4680-3p-specific inhibitor normalized cell proliferation and altered expression of ERBB2 and JADE1 in cells treated with atRA. Taken together, our results suggest that upregulation of miR-4680-3p induced by atRA may cause cleft palate through suppression of ERBB2 and JADE1. Thus, miRs may be potential targets for the prevention and diagnosis of cleft palate.

Regulation of c-ret expression by retinoic acid in rat metanephros: implication in nephron mass control

1998 ◽  
Vol 275 (6) ◽  
pp. F938-F945 ◽  
Author(s):  
Evelyne Moreau ◽  
José Vilar ◽  
Martine Lelièvre-Pégorier ◽  
Claudie Merlet-Bénichou ◽  
Thierry Gilbert
Keyword(s):  
Retinoic Acid ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Mrna Level ◽  
Cell Surface Receptor ◽  
Dependent Manner ◽  
All Trans Retinoic Acid ◽  
Surface Receptor ◽  
Dose Dependent

Vitamin A and its derivatives have been shown to promote kidney development in vitro in a dose-dependent fashion. To address the molecular mechanisms by which all- trans-retinoic acid (RA) may regulate the nephron mass, rat kidneys were removed on embryonic day 14( E14) and grown in organ culture under standard or RA-stimulated conditions. By using RT-PCR, we studied the expression of the glial cell line-derived neurotrophic factor (GDNF), its cell surface receptor-α (GDNFR-α), and the receptor tyrosine kinase c-ret, known to play a major role in renal organogenesis. Expression of GDNF and GDNFR-α transcripts was high at the time of explantation and remained unaffected in culture with or without RA. In contrast, c-ret mRNA level, which was low in E14 metanephros and dropped rapidly in vitro, was increased by RA in a dose-dependent manner. The same is true at the protein level. Exogenous GDNF barely promotes additional nephron formation in vitro. Thus the present data establish c-ret as a key target of retinoids during kidney organogenesis.

Relationship between retinoic acid and sonic hedgehog, two polarizing signals in the chick wing bud

Development ◽  
1994 ◽  
Vol 120 (11) ◽  
pp. 3267-3274 ◽  
Author(s):  
J. Helms ◽  
C. Thaller ◽  
G. Eichele
Keyword(s):  
Retinoic Acid ◽  
Sonic Hedgehog ◽  
Positional Information ◽  
Limb Bud ◽  
Dependent Manner ◽  
All Trans Retinoic Acid ◽  
Wing Bud ◽  
Zone Of Polarizing Activity ◽  
Dose Dependent

Local application of all-trans-retinoic acid (RA) to the anterior margin of chick limb buds results in pattern duplications reminescent of those that develop after grafting cells from the zone of polarizing activity (ZPA). RA may act directly by conferring positional information to limb bud cells, or it may act indirectly by creating a polarizing region in the tissue distal to the RA source. Here we demonstrate that tissue distal to an RA-releasing bead acquires polarizing activity in a dose-dependent manner. Treatments with pharmacological (beads soaked in 330 micrograms/ml) and physiological (beads soaked in 10 micrograms/ml) doses of RA are equally capable of inducing digit pattern duplication. Additionally, both treatments induce sonic hedgehog (shh; also known as vertebrate hedgehog-1, vhh-1), a putative ZPA morphogen and Hoxd-11, a gene induced by the polarizing signal. However, tissue transplantation assays reveal that pharmacological, but not physiological, doses create a polarizing region. This differential response could be explained if physiological doses induced less shh than pharmacological doses. However, our in situ hybridization analyses demonstrate that both treatments result in similar amounts of mRNA encoding this candidate ZPA morphogen. We outline a model describing the apparently disparate effects of pharmacologic and physiological doses RA on limb bud tissue.

scholarly journals 9-cis-retinoic acid is a natural antagonist for the retinoic acid receptor response pathway

1993 ◽  
Vol 295 (2) ◽  
pp. 343-346 ◽  
Author(s):  
C Carlberg ◽  
J H Saurat ◽  
G Siegenthaler
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptors ◽  
Dependent Manner ◽  
Receptor Response ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
X Receptors ◽  
Dose Dependent

The pleiotropic activities of retinoids are mediated by two types of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). All-trans-retinoic acid (RA) transcriptionally activates RARs, but not RXRs, whereas its natural stereoisomer, 9-cis-RA, is the ligand for RXRs. Here, we demonstrate that 9-cis-RA did not transcriptionally activate RARs, whereas in the presence of all-trans-RA the transactivation of RARs was inhibited in a dose-dependent manner by 9-cis-RA. RAR homodimer complexes were destabilized in vitro in the presence of 9-cis-RA. This suggests that 9-cis-RA may be a natural antagonist of all-trans-RA for binding to RAR complexes. The levels of 9-cis-RA may determine by which pathway the transcription of retinoid-responsive genes is modulated.

scholarly journals Cardiac Remodeling Induced by All-Trans Retinoic Acid is Detrimental in Normal Rats

2017 ◽  
Vol 43 (4) ◽  
pp. 1449-1459 ◽  
Author(s):  
Renata A. C. Silva ◽  
Andréa F. Gonçalves ◽  
Priscila P. dos Santos ◽  
Bruna Rafacho ◽  
Renan F. T. Claro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinoic Acid ◽  
Energy Metabolism ◽  
Cardiac Remodeling ◽  
Citrate Synthase ◽  
Isolated Heart ◽  
Lipid Hydroperoxide ◽  
Dependent Manner ◽  
Heart Study ◽  
Dose Dependent

Background/Aims: This study aimed to discern whether the cardiac alterations caused by retinoic acid (RA) in normal adult rats are physiologic or pathologic. Methods and Results: Wistar rats were assigned into four groups: control animals (C, n = 20) received a standard rat chow; animals fed a diet supplemented with 0.3 mg/kg/day all-trans-RA (AR1, n = 20); animals fed a diet supplemented with 5 mg/kg/day all-trans-RA (AR2, n = 20); and animals fed a diet supplemented with 10 mg/kg/day all-trans-RA (AR3, n = 20). After 2 months, the animals were submitted to echocardiogram, isolated heart study, histology, energy metabolism status, oxidative stress condition, and the signaling pathway involved in the cardiac remodeling induced by RA. RA increased myocyte cross-sectional area in a dose-dependent manner. The treatment did not change the morphological and functional variables, assessed by echocardiogram and isolated heart study. In contrast, RA changed catalases, superoxide dismutase, and glutathione peroxidases and was associated with increased values of lipid hydroperoxide, suggesting oxidative stress. RA also reduced citrate synthase, enzymatic mitochondrial complex II, ATP synthase, and enzymes of fatty acid metabolism and was associated with increased enzymes involved in glucose use. In addition, RA increased JNK 1/2 expression, without changes in TGF-β, PI3K, AKT, NFκB, S6K, and ERK. Conclusion: In normal rats, RA induces cardiac hypertrophy in a dose-dependent manner. The non-participation of the PI3K/Akt pathway, associated with the participation of the JNK pathway, oxidative stress, and changes in energy metabolism, suggests that cardiac remodeling induced by RA supplementation is deleterious.

VCAM-1 is a CS1 peptide-inhibitable adhesion molecule expressed by lymph node high endothelium

1993 ◽  
Vol 106 (1) ◽  
pp. 109-119 ◽  
Author(s):  
M.J. May ◽  
G. Entwistle ◽  
M.J. Humphries ◽  
A. Ager
Keyword(s):  
Lymph Node ◽  
Cell Interaction ◽  
Tnf Alpha ◽  
Dependent Manner ◽  
Ifn Gamma ◽  
Lymphocyte Adhesion ◽  
Peripheral Lymph ◽  
Endothelial Surface ◽  
Dose Dependent

Previous studies have shown that unactivated lymphocytes bind to CS1 peptide and that the adhesion of these cells to high endothelium is inhibited by CS1 peptide. These results suggest that lymphocyte binding occurs via recognition of the CS1-containing splice variant of fibronectin expressed on the high endothelial surface. We have now extended these studies by determining the role of the CS1 receptor, alpha 4 beta 1 (VLA-4) and the alternative VLA-4 ligand, VCAM-1 in a rat model of lymphocyte-high endothelial cell interaction. Anti-VLA-4 antibody, HP2/1, blocked lymphocyte adhesion to resting and IFN-gamma (interferon-gamma) pretreated cultured high endothelial cells (HEC) in a dose-dependent manner with maximal inhibition of 60%. HP2/1 completely blocked the adhesion of rat lymphocytes to immobilized CS1 peptide and to a recombinant soluble (rs) form of human VCAM-1. Lymphocyte binding to rsVCAM-1 was also completely blocked by CS1 peptide. Anti-rat VCAM-1 monoclonal antibody 5F10 inhibited adhesion to untreated and IFN-gamma-treated HEC equally and its effect at 50% inhibition was slightly less than that of HP2/1. These findings suggest that a CS1 peptide-inhibitable ligand expressed by high endothelium is VCAM-1. The majority of cultured HEC expressed significant levels of VCAM-1 under basal conditions, as did HEV in peripheral lymph nodes. VCAM-1 expression by HEC was upregulated by cytokine pretreatment and the effects were ordered: IFN-gamma > TNF-alpha > IL-1 beta. The results described here demonstrate that rat peripheral lymph node HEC express VCAM-1, its expression is upregulated by cytokines, in particular IFN-gamma, and it supports the adhesion of unactivated lymphocytes. They also suggest that the VLA-4/VCAM-1 adhesion pathway may operate during the constitutive migration of lymphocytes into lymphoid organs. Although the mechanism of CS1 peptide inhibition was not determined, these results show that VCAM-1 is a CS1 peptide-inhibitable ligand and therefore CS1, on its own, cannot be used as a specific indicator of fibronectin activity.

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