All-trans retinoic acid suppresses interleukin-6 expression in interleukin-1-stimulated synovial fibroblasts by inhibition of ERK1/2 pathway independently of RAR activation

Kirchmeyer, Mélanie; Koufany, Meriem; Sébillaud, Sylvie; Netter, Patrick; Jouzeau, Jean‐Yves; Bianchi, Arnaud

doi:10.1186/ar2569

Cited by 39 publications

(34 citation statements)

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“…For instance by IPA, p38 MAPK is activated by phospholipase C [44], Cdc42 [45], and LXR/RXR [46] signaling. Although initially identified as a protein kinase activated by stress, p38 MAPK signaling coordinates cellular responses during erythropoiesis [47].…”

Section: Resultsmentioning

confidence: 99%

Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

Ding

et al. 2012

BMC Genomics

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BackgroundThe fetal and adult globin genes in the human β-globin cluster on chromosome 11 are sequentially expressed to achieve normal hemoglobin switching during human development. The pharmacological induction of fetal γ-globin (HBG) to replace abnormal adult sickle βS-globin is a successful strategy to treat sickle cell disease; however the molecular mechanism of γ-gene silencing after birth is not fully understood. Therefore, we performed global gene expression profiling using primary erythroid progenitors grown from human peripheral blood mononuclear cells to characterize gene expression patterns during the γ-globin to β-globin (γ/β) switch observed throughout in vitro erythroid differentiation.ResultsWe confirmed erythroid maturation in our culture system using cell morphologic features defined by Giemsa staining and the γ/β-globin switch by reverse transcription-quantitative PCR (RT-qPCR) analysis. We observed maximal γ-globin expression at day 7 with a switch to a predominance of β-globin expression by day 28 and the γ/β-globin switch occurred around day 21. Expression patterns for transcription factors including GATA1, GATA2, KLF1 and NFE2 confirmed our system produced the expected pattern of expression based on the known function of these factors in globin gene regulation. Subsequent gene expression profiling was performed with RNA isolated from progenitors harvested at day 7, 14, 21, and 28 in culture. Three major gene profiles were generated by Principal Component Analysis (PCA). For profile-1 genes, where expression decreased from day 7 to day 28, we identified 2,102 genes down-regulated > 1.5-fold. Ingenuity pathway analysis (IPA) for profile-1 genes demonstrated involvement of the Cdc42, phospholipase C, NF-Kβ, Interleukin-4, and p38 mitogen activated protein kinase (MAPK) signaling pathways. Transcription factors known to be involved in γ-and β-globin regulation were identified.The same approach was used to generate profile-2 genes where expression was up-regulated over 28 days in culture. IPA for the 2,437 genes with > 1.5-fold induction identified the mitotic roles of polo-like kinase, aryl hydrocarbon receptor, cell cycle control, and ATM (Ataxia Telangiectasia Mutated Protein) signaling pathways; transcription factors identified included KLF1, GATA1 and NFE2 among others. Finally, profile-3 was generated from 1,579 genes with maximal expression at day 21, around the time of the γ/β-globin switch. IPA identified associations with cell cycle control, ATM, and aryl hydrocarbon receptor signaling pathways.ConclusionsThe transcriptome analysis completed with erythroid progenitors grown in vitro identified groups of genes with distinct expression profiles, which function in metabolic pathways associated with cell survival, hematopoiesis, blood cells activation, and inflammatory responses. This study represents the first report of a transcriptome analysis in human primary erythroid progenitors to identify transcription factors involved in hemoglobin switching. Our results also demonstrate that the in...

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Section: Resultsmentioning

confidence: 99%

Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

Ding

et al. 2012

BMC Genomics

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“…RA exists in three main stereoisomeric forms, all-trans-retinoic acid (atRA), 13-cis RA, and 9-cis RA, among which atRA is the primary biologically active form in brain. RA also exerts anti-inflammatory efficacy via repressing the expression of inflammatory factors such as IL-6, IL-12, and TNF␣ (13)(14)(15)(16) and modulating NFB signaling (17,18).…”

mentioning

confidence: 99%

“…Here we aim to investigate the potential modulation of BACE1 expression by RA and its underlying mechanism. Based on the known potent modulatory role of RA in immune response (13)(14)(15)(16), we speculated that RA might be able to suppress BACE1 expression under inflammatory conditions. It should be stressed that in comparison with the peripheral system, the anti-inflammatory role of RA in CNS remains largely elusive.…”

mentioning

confidence: 99%

All-trans-retinoic Acid Reduces BACE1 Expression under Inflammatory Conditions via Modulation of Nuclear Factor κB (NFκB) Signaling

Wang

Chen

Liu

et al. 2015

Journal of Biological Chemistry

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Background: BACE1 is the rate-limiting enzyme in the cleavage of amyloid precursor protein to A␤ peptides. Results: Retinoic acid blocks the BACE1 gene up-regulation during inflammation via the inhibition of NFB. Conclusion: Retinoic acid suppresses aspects of neuroinflammation in rodent models of Alzheimer disease including elevated BACE1 transcription. Significance: Retinoids may have an important role in limiting progression of Alzheimer disease.

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“…In addition, main immediate early antigens (IEA) were found to increase the enhancer acitivity of interleukin 6 (1,30) and ATRA was found to inhibit interleukin 6 via its receptors (31). Thus, it is presumable that the inhibitory effect of ATRA on interleukin 6 via ATRA receptors may relieve HCMV infection to some degree.…”

Section: Discussionmentioning

confidence: 99%

Effect of human cytomegalovirus infection on the expression of Hoxb2 and Hoxb4 genes in the developmental process of cord blood erythroid progenitors

Chen

2011

Mol Med Report

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Abstract. The aim of the present study was to investigate the role of Hoxb2 and Hoxb4 gene expression induced by human cytomegalovirus (HCMV) and/or all-trans retinoic acid (ATRA) on the proliferation and committed differentiation process of human cord blood hematopoietic stem cells (HSCs) to colony-forming erythroid progenitor cells (CFU-Es) in vitro. Cord blood was collected from the fetal placenta umbilical vein in 12 cases and cultured using hematopoietic stem cell culture technique in vitro. The proliferation and differentiation of cord blood HSCs to CFU-Es were continuously disrupted with HCMV-AD169 and/or 6x10 -8 mol/l of ATRA. Expression levels of the Hoxb2 and Hoxb4 genes in the blank, ATRA, HCMV-AD169 and ATRA + HCMV treatment groups of CFU-Es were detected on day 3, 7 and 10 of culture by fluorescent quantitative reverse transcriptase-polymerase chain reaction method. Hoxb2 and Hoxb4 gene expression in each group began on day 3, obviously increased on day 7 and reached a peak on day 10. The expression levels of the Hoxb2 and Hoxb4 genes in the HCMV group were obviously down-regulated compared with the level in the blank group. However, expression levels of the Hoxb2 and Hoxb4 genes were significantly up-regulated in the HCMV + ATRA group compared with the HCMV group (P<0.05). Abnormal expression of the Hoxb2 and Hoxb4 genes induced by HCMV may play important roles in abnormal hematopoietic damage. They were also correlated with the process of erythroid hematopoiesis. ATRA (6x10 -8 mol/l) significantly up-regulated expression of the Hoxb2 and Hoxb4 genes in the normal erythroid progenitor cells and in those cells infected with HCMV as well. IntroductionHuman cytomegalovirus (HCMV) is one of the most prevalent infective factors among the population worldwide. HCMV together with toxoplasm, rubella virus, herpes simplex virus and treponema pallidum are regarded as five biological teratogenic factors. The incidence rates of HCMV infection have reached 80-90% among the Chinese (1), which is even higher among children. Numerous studies have shown that the hematopoietic system is one of the major organs suffering from HCMV infection. We found that HCMV directly damages hematopoietic progenitor cells and leads to abnormal expression of the homeobox gene (Hox) in infected cells (2-9). Recent studies have shown that the Hox gene is associated with the development of hematopoietic cells and directly affects the proliferation, differentiation and maturity of hematopoietic stem cells due to structural and functional alterations. Hoxb2 and Hoxb4 genes are considered to be the major regulatory factors in the proliferation and differentiation process of erythroid cells (10,11). Meanwhile, the expression of the Hox genes can be regulated by all-trans retinoic acid (ATRA). In the present study, the role of the expression of the Hoxb2 and Hoxb4 genes was assessed in the proliferation and committed differentiation process of human cord blood hematopoietic stem cells to colony-forming erythroid progenitor cells (CFUEs), an...

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All-trans retinoic acid suppresses interleukin-6 expression in interleukin-1-stimulated synovial fibroblasts by inhibition of ERK1/2 pathway independently of RAR activation

Cited by 39 publications

References 46 publications

Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

All-trans-retinoic Acid Reduces BACE1 Expression under Inflammatory Conditions via Modulation of Nuclear Factor κB (NFκB) Signaling

Effect of human cytomegalovirus infection on the expression of Hoxb2 and Hoxb4 genes in the developmental process of cord blood erythroid progenitors

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