Inflammation is a ubiquitous factor accompanying normal aging and neurodegeneration, and recent studies indicate a major contribution of inducible cyclooxygenase (COX-2) and its downstream prostaglandin signaling pathways in modulating neuroinflammatory responses and neuronal function. We have previously shown that the prostaglandin PGE receptor EP4 suppresses innate immune responses in models of systemic inflammation. Here we investigated the role of the EP4 receptor in models of Parkinson's disease (PD). Systemic co-administration of the EP4 agonist ONO-AE1-329 with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prevented loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) without significant changes in glial activation, suggesting a potent neuroprotective effect of EP4 signaling in this acute model of DA neuronal loss. Cell-specific conditional ablation of EP4 in Cd11bCre;EP4 mice exacerbated MPTP-associated glial activation and T-cell infiltration in SNpc, consistent with anti-inflammatory functions of microglial EP4 signaling. In vitro, in primary microglia stimulated with oligomeric α-synuclein, EP4 receptor activation suppressed generation of pro-inflammatory and oxidative stress factors. Taken together, these findings suggest a dual neuroprotective and anti-inflammatory mechanism of action by the EP4 receptor in models of PD.
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http://dx.doi.org/10.1007/s11481-016-9713-6 | DOI Listing |
Int J Mol Sci
December 2024
Department of Physiology and Cell Biology, School of Medicine, University of Nevada Reno, Reno, NV 89557, USA.
The urothelium and lamina propria (LP) contribute to sensations of bladder fullness by releasing multiple mediators, including prostaglandins (PGs) and adenosine 5'-triphosphate (ATP), that activate or modulate functions of cells throughout the bladder wall. Mediators that are simultaneously released in response to bladder distention likely influence each other's mechanisms of release and action. This study investigated whether PGs could alter the extracellular hydrolysis of ATP by soluble nucleotidases (s-NTDs) released in the LP of nondistended or distended bladders.
View Article and Find Full Text PDFMolecules
December 2024
Graduate School of Pharmaceutical Sciences, Hiroshima International University, 5-1-1, Hirokoshingai, Kure 737-0112, Japan.
Farnesoid X receptor (FXR), a nuclear receptor, is expressed in calvaria and bone marrow stromal cells and plays a role in bone homeostasis. However, the mechanism of FXR-activated osteoblast differentiation remains unclear. In this study, we investigated the regulatory mechanism underlying FXR-activated osteoblast differentiation using bone morphogenetic protein-2 (BMP-2)-induced mouse ST-2 mesenchymal stem cells.
View Article and Find Full Text PDFAntioxidants (Basel)
December 2024
Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, 8010 Graz, Austria.
Endothelial dysfunction is a hallmark of several pathological conditions, including cancer, cardiovascular disease and inflammatory disorders. In these conditions, perturbed TCA cycle and subsequent succinate accumulation have been reported. The role of succinate as a regulator of immunological responses and inflammation is increasingly being recognized.
View Article and Find Full Text PDFBrain Behav Immun
December 2024
Wolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. Electronic address:
Angiotensin II is well known to have an important influence on blood pressure, mediated via the angiotensin II type 1 receptor (AT1R), but more recent studies have shown that angiotensin II may play an important additional role in eliciting pain via a distinct action at the angiotensin II type 2 receptor (AT2R). Signalling pathways that link activation of AT2R to a sensation of pain are, however, incompletely understood. Here we use rodent inflammatory pain models to confirm that selective activation of AT2R triggers aversive responses, and that these are abolished by either antagonism or genetic deletion of AT2R.
View Article and Find Full Text PDFEnviron Microbiol
December 2024
School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
Oxylipin signalling is central in biology, mediating processes such as cellular homeostasis, inflammation and molecular signalling. It may also facilitate inter-partner communication in the cnidarian-dinoflagellate symbiosis, though this aspect remains understudied. In this study, four oxylipin receptors were characterised using immunohistochemistry and immunoblotting in the sea anemone Exaiptasia diaphana ('Aiptasia'): Prostaglandin E2 receptor 2 (EP2) and 4 (EP4), Transient Receptor Potential cation channel A1 (TRPA1) and Glutamate Receptor Ionotropic, Kainate 2 (GRIK2).
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