scholarly journals Regulation of peroxisome proliferator-activated receptor β/δ expression and activity levels by toll-like receptor agonists and MAP kinase inhibitors in rat astrocytes

2014 ◽  
Vol 130 (4) ◽  
pp. 563-574 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Stepan Aleshin ◽  
Marina G. Sergeeva ◽  
Georg Reiser
Keyword(s):  
Map Kinase ◽  
Kinase Inhibitors ◽  
Peroxisome Proliferator ◽  
Activity Levels ◽  
Toll Like Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Agonists ◽  
Rat Astrocytes ◽  
Expression And Activity

PPAR-γ agonists inhibit toll-like receptor-mediated activation of dendritic cells via the MAP kinase and NF-κB pathways

Blood ◽  
2005 ◽  
Vol 106 (12) ◽  
pp. 3888-3894 ◽  
Author(s):  
Silke Appel ◽  
Valdete Mirakaj ◽  
Anita Bringmann ◽  
Markus M. Weck ◽  
Frank Grünebach ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Map Kinase ◽  
Lymphocyte Activation ◽  
Human Monocyte ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Toll Like Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cytokines And Chemokines

Dendritic cells (DCs) play an important role in initiating and maintaining primary immune responses. However, mechanisms involved in the resolution of these responses are elusive. We analyzed the effects of 15d-PGJ2 and the synthetic peroxisome proliferator-activated receptor (PPAR)-γ ligand troglitazone (TGZ) on the immunogenicity of human monocyte-derived DCs upon stimulation with toll-like receptor (TLR) ligands. Activation of PPAR-γ resulted in a reduced stimulation of DCs via the TLR ligands 2, 3, 4, and 7, characterized by down-regulation of costimulatory and adhesion molecules and reduced secretion of cytokines and chemokines involved in T-lymphocyte activation and recruitment. MCP-1 (monocyte chemotactic protein-1) production was increased due to PPAR-γ activation. Furthermore, TGZ-treated DCs showed a significantly reduced capacity to stimulate T-cell proliferation, emphasizing the inhibitory effect of PPAR-γ activation on TLR-induced DC maturation. Western blot analyses revealed that these inhibitory effects on TLR-induced DC activation were mediated via inhibition of the NF-κB and mitogen-activated protein (MAP) kinase pathways while not affecting the PI3 kinase/Akt signaling. Our data demonstrate that inhibition of the MAP kinase and NF-κB pathways is critically involved in the regulation of TLR and PPAR-γ-mediated signaling in DCs.

scholarly journals Peroxisome proliferator-activated receptor α-retinoid X receptor agonists induce beta-cell protection against palmitate toxicity

FEBS Journal ◽  
2007 ◽  
Vol 274 (23) ◽  
pp. 6094-6105 ◽  
Author(s):  
Karine Hellemans ◽  
Karen Kerckhofs ◽  
Jean-Claude Hannaert ◽  
Geert Martens ◽  
Paul Van Veldhoven ◽  
...  
Keyword(s):  
Beta Cell ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Cell Protection ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Agonists ◽  
Beta Cell Protection

scholarly journals Activation of Peroxisome Proliferator-activated Receptor α (PPARα) Suppresses Hypoxia-inducible Factor-1α (HIF-1α) Signaling in Cancer Cells

2012 ◽  
Vol 287 (42) ◽  
pp. 35161-35169 ◽  
Author(s):  
Jundong Zhou ◽  
Shuyu Zhang ◽  
Jing Xue ◽  
Jori Avery ◽  
Jinchang Wu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Proteasome Inhibitors ◽  
Tube Formation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoxia Inducible Factor 1Α ◽  
Anticancer Properties ◽  
Pparγ Agonist ◽  
Expression And Activity

Activation of peroxisome proliferator-activated receptor α (PPARα) has been demonstrated to inhibit tumor growth and angiogenesis, yet the mechanisms behind these actions remain to be characterized. In this study, we examined the effects of PPARα activation on the hypoxia-inducible factor-1α (HIF-1α) signaling pathway in human breast (MCF-7) and ovarian (A2780) cancer cells under hypoxia. Incubation of cancer cells under 1% oxygen for 16 h significantly induced HIF-1α expression and activity as assayed by Western blotting and reporter gene analysis. Treatment of the cells with PPARα agonists, but not a PPARγ agonist, prior to hypoxia diminished hypoxia-induced HIF-1α expression and activity, and addition of a PPARα antagonist attenuated the suppression of HIF-1α signaling. Activation of PPARα attenuated hypoxia-induced HA-tagged HIF-1α protein expression without affecting the HA-tagged HIF-1α mutant protein level, indicating that PPARα activation promotes HIF-1α degradation in these cells. This was further confirmed using proteasome inhibitors, which reversed PPARα-mediated suppression of HIF-1α expression under hypoxia. Using the co-immunoprecipitation technique, we found that activation of PPARα enhances the binding of HIF-1α to von Hippel-Lindau tumor suppressor (pVHL), a protein known to mediate HIF-1α degradation through the ubiquitin-proteasome pathway. Following PPARα-mediated suppression of HIF-1α signaling, VEGF secretion from the cancer cells was significantly reduced, and tube formation by endothelial cells was dramatically impaired. Taken together, these findings demonstrate for the first time that activation of PPARα suppresses hypoxia-induced HIF-1α signaling in cancer cells, providing novel insight into the anticancer properties of PPARα agonists.

scholarly journals The future of bronchodilation: looking for new classes of bronchodilators

2019 ◽  
Vol 28 (154) ◽  
pp. 190095 ◽  
Author(s):  
Mario Cazzola ◽  
Paola Rogliani ◽  
Maria Gabriella Matera
Keyword(s):  
Kinase Inhibitors ◽  
Taste Receptor ◽  
Rho Kinase ◽  
Soluble Guanylyl Cyclase ◽  
Phosphodiesterase Inhibitors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Preclinical Phase ◽  
Rho Kinase Inhibitors ◽  
The Impact

Available bronchodilators can satisfy many of the needs of patients suffering from airway disorders, but they often do not relieve symptoms and their long-term use raises safety concerns. Therefore, there is interest in developing new classes that could help to overcome the limits that characterise the existing classes.At least nine potential new classes of bronchodilators have been identified: 1) selective phosphodiesterase inhibitors; 2) bitter-taste receptor agonists; 3) E-prostanoid receptor 4 agonists; 4) Rho kinase inhibitors; 5) calcilytics; 6) agonists of peroxisome proliferator-activated receptor-γ; 7) agonists of relaxin receptor 1; 8) soluble guanylyl cyclase activators; and 9) pepducins. They are under consideration, but they are mostly in a preclinical phase and, consequently, we still do not know which classes will actually be developed for clinical use and whether it will be proven that a possible clinical benefit outweighs the impact of any adverse effect.It is likely that if developed, these new classes may be a useful addition to, rather than a substitution of, the bronchodilator therapy currently used, in order to achieve further optimisation of bronchodilation.

scholarly journals Evaluation of peroxisome proliferator-activated receptor agonists on interleukin-5-induced eosinophil differentiation

Immunology ◽  
2014 ◽  
Vol 142 (3) ◽  
pp. 484-491 ◽  
Author(s):  
Steven G. Smith ◽  
Mike Hill ◽  
John-Paul Oliveria ◽  
Brittany M. Watson ◽  
Adrian J. Baatjes ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interleukin 5 ◽  
Receptor Agonists
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