Retinoic acid modulation of mucin mRNA in rat tracheal explants: Response to actinomycin D, cycloheximide, signal transduction effectors and antisense oligodeoxynucleotide

Inflammation ◽  
1994 ◽  
Vol 18 (6) ◽  
pp. 565-574 ◽  
Author(s):  
Sambhu N. Bhattacharyya ◽  
Patrick Ashbaugh ◽  
Bernard Kaufman ◽  
Brigitta Manna
Keyword(s):  
Signal Transduction ◽  
Retinoic Acid ◽  
Actinomycin D ◽  
Antisense Oligodeoxynucleotide ◽  
Tracheal Explants

Retinoic Acid Signal Transduction Pathways

1993 ◽  
Vol 684 (1 Zinc-Finger P) ◽  
pp. 19-34 ◽  
Author(s):  
MARK LEID ◽  
PHILIPPE KASTNER ◽  
BÉATRICE DURAND ◽  
ANDRÉE KRUST ◽  
PIERRE LEROY ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Retinoic Acid ◽  
Signal Transduction Pathways

scholarly journals Retinoic acid inhibits interleukin-6-induced macrophage differentiation and apoptosis in a murine hematopoietic cell line, Y6

Blood ◽  
1992 ◽  
Vol 80 (9) ◽  
pp. 2298-2305 ◽  
Author(s):  
K Oritani ◽  
T Kaisho ◽  
K Nakajima ◽  
T Hirano
Keyword(s):  
Signal Transduction ◽  
Retinoic Acid ◽  
Cell Line ◽  
Interleukin 6 ◽  
Signal Transduction Pathway ◽  
Inhibitory Effect ◽  
Hematopoietic Cell ◽  
Transduction Pathway ◽  
Macrophage Differentiation ◽  
Hematopoietic Cell Line

Abstract We established a radiation-induced murine hematopoietic cell line, Y6, that could be induced to differentiate into macrophages by interleukin- 6 (IL-6). IL-6 also induced growth inhibition and apoptosis in Y6 cells. Retinoic acid (RA) inhibited such effects of IL-6 on Y6 cells. The inhibitory effect of RA on the effects of IL-6 was not caused by the downregulation of the IL-6 receptor, because RA neither affected the expression of IL-6 receptor mRNA nor the expression of IL-6 receptor molecule on the cell surface. Furthermore, RA did not inhibit the IL-6-induced expression of junB mRNA, indicating that the expression of functionally active IL-6 receptor and the signal transduction pathway activating the junB gene are not inhibited by RA. IL-6-induced macrophage differentiation of Y6 cells was preceded by the downregulation of the c-myc gene, which was also prevented by RA. Because the inhibitory effect of RA on Y6 cells was reversible and seemed not to require de novo protein synthesis, the RA receptor by itself might be directly involved in the inhibition of the IL-6 signal transduction pathway. The results indicated that the IL-6 signal transduction pathways leading to the induction of macrophage differentiation and junB gene expression can be dissected by RA.

scholarly journals Opposing effects of tumour necrosis factor α and hyperosmolarity on Na+/myo-inositol co-transporter mRNA levels and myo-inositol accumulation by 3T3-L1 adipocytes

1998 ◽  
Vol 336 (2) ◽  
pp. 317-325 ◽  
Author(s):  
Mark A. YOREK ◽  
Joyce A. DUNLAP ◽  
William L. LOWE
Keyword(s):  
Signal Transduction ◽  
Tumour Necrosis ◽  
Actinomycin D ◽  
Signal Transduction Pathways ◽  
Mrna Levels ◽  
Tumour Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Opposing Effects ◽  
Necrosis Factor

Tumour necrosis factor α (TNF-α) regulates the transport of myo-inositol in 3T3-L1 adipocytes. Treating 3T3-L1 adipocytes with TNF-α decreases Na+/myo-inositol co-transporter (SMIT) mRNA levels and myo-inositol accumulation in a concentration-and time-dependent manner. TNF-α decreases the V′max for high-affinity myo-inositol transport with little change in the K′m. Studies with actinomycin D suggest that RNA synthesis is required for the TNF-α-induced effect on SMIT mRNA levels. In contrast with the effect of TNF-α, hyperosmolarity increases SMIT mRNA levels and myo-inositol accumulation in 3T3-L1 adipocytes. Hyperosmolarity increases SMIT gene expression as evidenced by the inhibition of hyperosmotic induction of SMIT mRNA levels by actinomycin D, and of myo-inositol accumulation by actinomycin D and cycloheximide. TNF-α and osmotic stress have previously been shown to activate similar signal transduction pathways in mammalian cells. In 3T3-L1 adipocytes, both TNF-α and hyperosmolarity increase mitogen-activated protein kinase kinase pathway activity; however, with the possible exception of c-Jun N-terminal kinase, this pathway does not seem to regulate SMIT mRNA levels or myo-inositol accumulation. TNF-α activates nuclear factor κB (NF-κB) in 3T3-L1 adipocytes but, unlike the effect of TNF-α on cultured endothelial cells, NF-κB does not seem to contribute to the regulation by TNF-α of SMIT gene expression in 3T3-L1 adipocytes. Therefore other signal transduction pathways must be considered in the regulation by TNF-α of SMIT mRNA levels and activity. Thus TNF-α and hyperosmolarity have opposing effects on SMIT mRNA levels and activity in 3T3-L1 adipocytes. Because myo-inositol in the form of phosphoinositides is an important component of membranes and signal transduction pathways, the regulation of myo-inositol metabolism by TNF-α might represent another mechanism by which TNF-α regulates adipocyte function.

Ligand-bound RXR can mediate retinoid signal transduction during embryogenesis

Development ◽  
1997 ◽  
Vol 124 (1) ◽  
pp. 195-203 ◽  
Author(s):  
H.C. Lu ◽  
G. Eichele ◽  
C. Thaller
Keyword(s):  
Signal Transduction ◽  
Retinoic Acid ◽  
Experimental System ◽  
Limb Bud ◽  
Retinoic Acid Receptors ◽  
Vertebrate Development ◽  
High Affinity ◽  
X Receptors ◽  
Complex Expression

Retinoids regulate various aspects of vertebrate development through the action of two types of receptors, the retinoic acid receptors (RARs) and the retinoid-X-receptors (RXRs). Although RXRs bind 9-cis-retinoic acid (9cRA) with high affinity, in vitro experiments suggest that RXRs are for the most part not liganded, but serve as auxiliary factors forming heterodimers with liganded partner receptors such as RAR. Here we have used RXR- and RAR-specific ligands 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-napthyl)ethenyl]b enzoic acid (LG69) and (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1-prope nyl]benzoic acid (TTNPB), and show that, in the context of an embryo, liganded RXR can mediate retinoid signal transduction. This conclusion emerges from examining the induction of several retinoid-responsive genes in the limb bud (Hoxb-6/-8, RARbeta) and in the developing central nervous system (Hoxb-1, otx-2). RARbeta and Hoxb-1 genes were most effectively activated by a combination of TTNPB and LG69, suggesting that the activation of these genes benefits from the presence of ligand-bound RAR and ligand-bound RXR. Hoxb-6/-8 genes were most efficiently induced by LG69, suggesting that liganded RXR can activate these genes. The regulation of the expression of the otx-2 gene was complex; expression was repressed by TTNPB, but such repression was relieved when LG69 was provided together with TTNPB, suggesting that ligand-bound RXR can overcome repression of transcription exerted by liganded RAR. Based on these findings, we propose that in our experimental system in which ligands are provided exogenously, transcriptional regulation of several genes involves liganded RXR.

scholarly journals Retinoic acid and dexamethasone affect RAR-β and surfactant protein C mRNA in the MLE lung cell line

1998 ◽  
Vol 274 (1) ◽  
pp. L1-L7 ◽  
Author(s):  
Mary A. Grummer ◽  
Richard D. Zachman
Keyword(s):  
Retinoic Acid ◽  
Cell Line ◽  
Lung Development ◽  
Actinomycin D ◽  
Surfactant Protein ◽  
Mouse Lung ◽  
Epithelial Cell Line ◽  
Surfactant Protein C ◽  
Lung Epithelial ◽  
Lung Cell Line

Lung development and surfactant biosynthesis are affected by retinoic acid (RA) and dexamethasone (Dex). Using a mouse lung epithelial cell line, we are exploring RA-Dex interactions through the study of RA and Dex effects on RA receptor (RAR) and surfactant protein (SP) C mRNA expression. RA increased expression of RAR-β (5.5 times) and SP-C (2 times) mRNA, with maximal effects at 24 h and at 10−6 M. The RA induction was not inhibited by cycloheximide, suggesting RA affects transcription. With added actinomycin D, RA did not affect the disappearance rate of RAR-β mRNA, but SP-C mRNA degradation was slowed, indicating an effect on SP-C mRNA stability. Dex decreased RAR-β and SP-C expression to 75 and 70% of control values, respectively, with greatest effects at 48 h and at 10−7 M. There was no effect of Dex on either RAR-β or SP-C mRNA disappearance with actinomycin D. However, cycloheximide prevented the effect of Dex. Despite Dex, RA increased both RAR-β and SP-C mRNA. This work suggests that RA and Dex affect RAR-β and SP-C genes by different mechanisms.

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