Retinoic acid suppresses interleukin-6 production in human endometrial cells

2000 ◽  
Vol 73 (5) ◽  
pp. 1012-1019 ◽  
Author(s):  
Sayan Sawatsri ◽  
Nina Desai ◽  
John A Rock ◽  
Neil Sidell
Keyword(s):  
Retinoic Acid ◽  
Interleukin 6 ◽  
Endometrial Cells

Retinoid regulation of interleukin-6 in human endometrial cells

1998 ◽  
Vol 5 (1) ◽  
pp. 108A-108A
Author(s):  
S SAWATSRI ◽  
R RAZDAN ◽  
N DESAI ◽  
N SIDELL
Keyword(s):  
Interleukin 6 ◽  
Endometrial Cells

scholarly journals Inhibition of myeloma cell growth by dexamethasone and all-trans retinoic acid: synergy through modulation of interleukin-6 autocrine loop at multiple sites

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 314-323 ◽  
Author(s):  
YH Chen ◽  
P Desai ◽  
RT Shiao ◽  
D Lavelle ◽  
A Haleem ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Growth ◽  
Mrna Expression ◽  
Interleukin 6 ◽  
Growth Regulation ◽  
Myeloma Cell ◽  
Myeloma Cells ◽  
Trans Retinoic Acid ◽  
Clonogenic Growth ◽  
All Trans Retinoic Acid

Abstract Interleukin-6 (IL-6)/IL-6 receptor (IL-6R) plays a major role in autocrine/paracrine growth regulation of myeloma cells. We investigated the effect of dexamethasone and all-trans retinoic acid, previously shown to modulate IL-6/IL-6R, on the in vitro growth of a human myeloma cell line, OPM-2. Both agents inhibited the clonogenic growth and 3H- thymidine incorporation in a concentration-dependent fashion. Isobologram and median effect analysis showed a strong synergy between these two agents with a combination index in the range of 0.2 to 0.6. Both agents decreased the labeling index and the cell fraction in S and G2/M phases, suggesting a block in G1-S phase transition. The clonogenic growth was stimulated by exogenous IL-6 and was inhibited by monoclonal antibody to IL-6, suggesting an autocrine function of IL-6. The effect of dexamethasone but not all-trans retinoic acid was completely reversed by exogenous IL-6. Dexamethasone increased, while all-trans retinoic acid reduced, IL-6R but not gp130 mRNA expression. Their combination caused a net reduction in IL-6R mRNA. Cellular IL-6R density was altered correspondingly without changes in the binding affinity. IL-6 mRNA expression was reduced by dexamethasone and the combination, but was not affected by retinoic acid alone. However, IL-6 secretion into culture supernatant was abolished by both agents. A survey of 4 additional human myeloma cells showed that 1 was sensitive to both, 1 was sensitive to one agent only, and 2 were resistant to both. The study demonstrates the possibility of regulating myeloma cell growth through modulation of IL-6/IL-6R autocrine/paracrine loop and the principle of achieving a synergistic effect by blocking this loop at multiple sites.

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 Altered Retinoid Uptake and Action Contributes to Cell Survival in Endometriosis

2010 ◽  
Vol 95 (11) ◽  
pp. E300-E309 ◽  
Author(s):  
Mary Ellen Pavone ◽  
Scott Reierstad ◽  
Hui Sun ◽  
Magdy Milad ◽  
Serdar E. Bulun ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Progesterone Receptor ◽  
Cell Survival ◽  
Stromal Cells ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Endometrial Stromal Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Endometrial Cells

Context: Retinoic acid (RA) controls multiple biological processes via exerting opposing effects on cell survival. Retinol uptake into cells is controlled by stimulated by RA 6 (STRA6). RA is then produced from retinol in the cytosol. Partitioning of RA between the nuclear receptors RA receptor α and peroxisome-proliferator-activated receptor β/δ is regulated by cytosol-to-nuclear shuttling proteins cellular RA binding protein 2 (CRABP2) and fatty acid binding protein 5 (FABP5), which induce apoptosis or enhance survival, respectively. The roles of these mechanisms in endometrium or endometriosis remain unknown. Objective: The aim was to determine the regulation of retinoid uptake and RA action in primary stromal cells from endometrium (n = 10) or endometriosis (n = 10). Results: Progesterone receptor was necessary for high STRA6 and CRABP2 expression in endometrial stromal cells. STRA6, which was responsible for labeled retinoid uptake, was strikingly lower in endometriotic cells compared to endometrial cells. CRABP2 knockdown in endometrial cells increased survival, and FABP5 knockdown in endometriotic cells decreased survival without altering the expression of downstream nuclear retinoic acid receptor α and peroxisome-proliferator-activated receptor β/δ. Conclusions: In endometrial stromal cells, progesterone receptor up-regulates expression of STRA6 and CRABP2, which control retinol uptake and growth-suppressor actions of RA. In endometriotic stromal cells, decreased expression of these genes leads to decreased retinol uptake and dominant FABP5-mediated prosurvival activity.

scholarly journals Inhibitory effect of all-trans retinoic acid on the growth of freshly isolated myeloma cells via interference with interleukin-6 signal transduction [see comments]

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3040-3046 ◽  
Author(s):  
A Ogata ◽  
N Nishimoto ◽  
Y Shima ◽  
K Yoshizaki ◽  
T Kishimoto
Keyword(s):  
Retinoic Acid ◽  
Stromal Cells ◽  
Interleukin 6 ◽  
Surface Expression ◽  
Myeloma Cell ◽  
Inhibitory Effect ◽  
Cell Surface Expression ◽  
Myeloma Cells ◽  
All Trans Retinoic Acid ◽  
Interleukin 6 Receptor

We showed the dose-dependent growth inhibition by alltrans retinoic acid (ATRA) of myeloma cells freshly isolated from patients. ATRA downregulated the cell surface expression of interleukin-6 receptor (IL- 6R) and/or glycoprotein (gp) 130. The growth-inhibitory activity of ATRA was well correlated with that of anti-gp 130 antibody in every sample. Furthermore, ATRA inhibited the production of IL-6 from both myeloma cells and marrow stromal cells, and recombinant IL-6 (rIL-6) could partially recover the myeloma cell growth that had been inhibited by ATRA. These data suggest that ATRA may inhibit the proliferation of myeloma cells both by the downregulation of IL-6R and gp130 expression on myeloma cells and by the inhibition of IL-6 production from myeloma and stromal cells. Prednisolone (PSL) and interferon-gamma (IFN-gamma) also inhibited the myeloma growth, while their effects were different from those of ATRA on IL-6 R and gp130 expression, IL-6 production, and morphological change. The inhibitory effect of ATRA on myeloma cell proliferation was observed in 10 of 14 samples obtained from eight patients, which suggests that ATRA may be a potent new therapeutic agent for some myeloma patients.

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