Down‐regulation of human CYP3A4 by the inflammatory signal interleukin 6: molecular mechanism and transcription factors involved

2002 ◽  
Vol 16 (13) ◽  
pp. 1-29 ◽  
Author(s):  
Ramiro Jover ◽  
Roque Bort ◽  
Ma. José Gómez‐Lechón ◽  
José V. Castell
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanism ◽  
Interleukin 6 ◽  
Down Regulation

scholarly journals Morphological Characterization of Flower Buds Development and Related Gene Expression Profiling at Bud Break Stage in Heterodichogamous Cyclocarya paliurus (Batal.) lljinskaja

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 818 ◽  
Author(s):  
Chen ◽  
Mao ◽  
Huang ◽  
Fang
Keyword(s):  
Transcription Factors ◽  
Molecular Mechanism ◽  
Mating Type ◽  
Southern China ◽  
Expression Patterns ◽  
Transcriptional Level ◽  
Bud Break ◽  
Illumina Hiseq ◽  
Cyclocarya Paliurus ◽  
Qrt Pcr

Cyclocarya paliurus (Batal.) Iljinskaja, a unique species growing in southern China, is a multi-function tree species with medicinal, healthcare, material, and ornamental values. So far, sexual reproduction is the main method for extensive cultivation of C. paliurus plantations, but this is limited by low seed plumpness resulted from the character of heterodichogamy. Phenological observations have revealed the asynchronism of flower development in this species. However, its molecular mechanism remains largely unknown. To reveal molecular mechanism of heterodichogamy in C. paliurus, transcriptome of female (F) and male (M) buds from two mating types (protandry, PA; protogyny, PG) at bud break stage were sequenced using Illumina Hiseq 4000 platform. The expression patterns of both 32 genes related to flowering and 58 differentially expressed transcription factors (DETFs) selected from 6 families were divided four groups (PG-F, PG-M, PA-F, and PA-M) into two categories: first flowers (PG-F and PA-M) and later flowers (PA-F and PG-M). The results indicated that genes related to plant hormones (IAA, ABA, and GA) synthesis and response, glucose metabolism, and transcription factors (especially in MIKC family) played significant roles in regulating asynchronism of male and female flowers in the same mating type. The expression of DETFs showed two patterns. One contained DETFs up-regulated in first flowers in comparison to later flowers, and the other was the reverse. Nine genes related to flowering were selected for qRT-PCR to confirm the accuracy of RNA-seq, and generally, the RPKM values of these genes were consistent with the result of qRT-PCR. The results of this work could improve our understanding in asynchronism of floral development within one mating type in C. paliurus at transcriptional level, as well as lay a foundation for further study in heterodichogamous plants.

scholarly journals HOXD8/DIAPH2-AS1 epigenetically regulates PAX3 and impairs HTR-8/SVneo cell function under hypoxia

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yaling Feng ◽  
Jianxia Wang ◽  
Yue He ◽  
Heng Zhang ◽  
Minhui Jiang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Rna Interference ◽  
Chromatin Immunoprecipitation ◽  
Regulatory Network ◽  
Molecular Basis ◽  
Promoter Region ◽  
Cell Function ◽  
Down Regulation ◽  
Histone 3 ◽  
Development Data

Abstract The present study aimed to unravel the molecular basis underlying PAX3 down-regulation, known to be involved in pre-eclampsia (PE) occurrence and development. Data obtained from databases suggested that Pax3 methylation levels in the promoter region are high in the placentas of PE patients. However, the expression of methylation-adjusting enzymes, including DNMT1, LSD1, and EZH2, did not change. Since lncRNAs enhance the function of methylation-related enzymes independently of expression, we selected three lncRNAs, RP11-269F21.2, DIAPH2-AS1, and RP11-445K13.2, predicted to interact with methylation-adjusting enzymes. Two transcription factors, HOXD8 and Lhx3, predicted to regulate the expression of lncRNAs, were also selected. Using RNA interference technology, HOXD8 and Lhx3 were found to positively regulate DIAPH2-AS1 and RP11-445K13.2 in HTR-8/SVneo cells. Chromatin immunoprecipitation assays determined that DIAPH2-AS1 recruited LSD1 to histone 3, increasing DNMT1 stability at H3. The HOXD8/DIAPH2-AS1 network regulated HTR-8/SVneo cell function under hypoxia by epigenetically regulating PAX3. This regulatory network may thus be responsible for PAX3 down-regulation in the placentas of PE patients.

scholarly journals Internalization of the interleukin 6 signal transducer gp130 does not require activation of the Jak/STAT pathway

1998 ◽  
Vol 330 (1) ◽  
pp. 47-54 ◽  
Author(s):  
Stefan THIEL ◽  
Iris BEHRMANN ◽  
Elke DITTRICH ◽  
Leon MUYS ◽  
Jan TAVERNIER ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Interleukin 6 ◽  
Tyrosine Kinases ◽  
Receptor Tyrosine Kinases ◽  
Signal Transducer ◽  
Down Regulation ◽  
Receptor System ◽  
Stat Proteins ◽  
Receptor Mediated Endocytosis ◽  
Stat Pathway

Signalling receptors often undergo receptor-mediated endocytosis. In many cases this internalization is stimulated by ligand binding and activation of intrinsic receptor tyrosine kinases, resulting in a receptor down-regulation. We have analysed whether internalization of the interleukin 6 signal transducer gp130 is dependent on the activation of receptor-associated Jak kinases. By using a chimaeric receptor system we found that receptor mutants that lack box1 and therefore are not capable of activating Jak and signal transducer and activator of transcription (STAT) proteins are still endocytosed efficiently. A chimaeric receptor with the recently identified dileucine internalization motif being replaced by two alanine residues was not efficiently internalized but still capable of recruiting STATs. Furthermore an antagonistic antibody that inhibits the signalling of all interleukin-6-type cytokines via gp130 was internalized as efficiently as an agonistic one that activates the Jak/STAT pathway. Our findings suggest that the endocytosis of gp130 is signal-independent.

Induction of Multilineage Markers in Human Myeloma Cells and Their Down-Regulation by Interleukin 6

2007 ◽  
Vol 85 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Shangqin Liu ◽  
Ken-ichiro Otsuyama ◽  
Zi Ma ◽  
Saeid Abroun ◽  
Karim Shamsasenjan ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Down Regulation ◽  
Myeloma Cells ◽  
Human Myeloma Cells

C/EBPβ Is a Critical Factor for Proliferation and Apoptosis in MM Cells by Controlling Transcription Factors Like IRF-4, PAX5 and Blimp1.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1506-1506
Author(s):  
Rekha Pal ◽  
Martin Janz ◽  
Deborah Galson ◽  
Suzanne Lentzsch
Keyword(s):  
Transcription Factors ◽  
Western Blot ◽  
Cell Lines ◽  
Plasma Cells ◽  
Annexin V ◽  
Critical Factor ◽  
Myeloma Cell ◽  
Down Regulation ◽  
Protein Levels ◽  
Rpmi 8226

Abstract The development and maturation of plasma cells is dictated by multiple interacting transcription factors (TFs). C/EBPb (NF-IL6) is a TF regulated by IL-6 and has profound effects on the regulation of growth, survival and differentiation of B-cells. Mice deficient in C/EBPb show impaired generation of B lymphocytes suggesting that C/EBPb plays an important role in B lymphopoiesis. In this study we delineated the effect of C/EBPb on transcription factors critical for myeloma cell proliferation by over-expressing and inhibiting C/EBPb in myeloma cells. Multiple myeloma (MM) cell lines MM.1S, RPMI-8226 and H929 were transiently transfected with GFP, C/EBPb (pcNF-IL6), and truncated C/EBPb with a deletion of the internal spII-spII fragment [pcmNF-IL6(Dspl)] by using Bio-Rad Gene Pulser Xcell, followed by G418 selection. A pool of transfected cells was selected and subjected to thymidine incorporation, flow cytometry and western blot analysis. We found that transfection of a truncated form of C/EBPb induced a down-regulation of C/EBPb in MM cell lines (MM.1S, RPMI-8226 and H929) as measured by western blot. Down-regulation of C/EBPβ significantly inhibited proliferation and induced apoptosis of MM cell lines analyzed by annexin V-FITC/PI staining. This was accompanied by a complete down-regulation of the anti-apoptotic protein BCL-2. Further, inhibition of C/EBPb completely decreased IRF-4 expression. In contrast, over-expression of C/EBPb increased protein levels of IRF-4 suggesting that IRF-4 is under control of C/EBPb. IRF-4, which was over-expressed in all our tested MM cells lines, is an essential TF for the generation of plasma cells by regulating TFs like Blimp-1 and PAX-5, which are critical for plasma cell differentiation. Our studies showed that down-regulation of IRF-4 resulted in a complete abrogation of Blimp-1 and PAX-5 suggesting that the expression of these factors is C/EBPb/IRF-4 dependent. In conclusion, our data indicate that C/EBPb is an important key regulator for survival and growth of MM cells. We show for the first time that C/EBPb is a critical regulator upstream of IRF-4. Down-regulation of the C/EBPb and consequently IRF-4 results in complete disruption of the network of TFs necessary for MM growth and survival. Targeting C/EBPb may provide a novel therapeutic approach in the treatment of MM.

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