Browsing by Subject "Prostaglandin"

Now showing 1 - 4 of 4
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    Differential Stem and Progenitor Cell Trafficking by Prostaglandin E2
    (Springer Nature, 2013) Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha; Hoggatt, Amber F.; Chitteti, Brahmananda Reddy; Speth, Jennifer M.; Hu, Peirong; Poteat, Bradley A.; Stilger, Kayla N.; Ferraro, Francesca; Silberstein, Lev; Wong, Frankie K.; Farag, Sherif S.; Czader, Magdalena; Milne, Ginger L.; Breyer, Richard M.; Serezani, Carlos H.; Scadden, David T.; Guise, Theresa; Srour, Edward F.; Pelus, Louis M.; Medicine, School of Medicine
    To maintain lifelong production of blood cells, haematopoietic stem cells (HSCs) are tightly regulated by inherent programs and extrinsic regulatory signals received from their microenvironmental niche. Long-term repopulating HSCs reside in several, perhaps overlapping, niches that produce regulatory molecules and signals necessary for homeostasis and for increased output after stress or injury. Despite considerable advances in the specific cellular or molecular mechanisms governing HSC-niche interactions, little is known about the regulatory function in the intact mammalian haematopoietic niche. Recently, we and others described a positive regulatory role for prostaglandin E2 (PGE2) on HSC function ex vivo. Here we show that inhibition of endogenous PGE2 by non-steroidal anti-inflammatory drug (NSAID) treatment in mice results in modest HSC egress from the bone marrow. Surprisingly, this was independent of the SDF-1-CXCR4 axis implicated in stem-cell migration. Stem and progenitor cells were found to have differing mechanisms of egress, with HSC transit to the periphery dependent on niche attenuation and reduction in the retentive molecule osteopontin. Haematopoietic grafts mobilized with NSAIDs had superior repopulating ability and long-term engraftment. Treatment of non-human primates and healthy human volunteers confirmed NSAID-mediated egress in other species. PGE2 receptor knockout mice demonstrated that progenitor expansion and stem/progenitor egress resulted from reduced E-prostanoid 4 (EP4) receptor signalling. These results not only uncover unique regulatory roles for EP4 signalling in HSC retention in the niche, but also define a rapidly translatable strategy to enhance transplantation therapeutically.
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    Omidenepag isopropyl ophthalmic solution for open-angle glaucoma and ocular hypertension: an update
    (Taylor & Francis, 2021) Aihara, Makoto; Aung, Tin; Bacharach, Jason; Cantor, Louis; Kook, Michael; Nakazawa, Toru; Park, Ki Ho; Lu, Da-Wen; Ophthalmology, School of Medicine
    Introduction: Current medical therapy for glaucoma consists of topical agents that lower intraocular pressure (IOP). Prostaglandin F2α analogues, the most commonly used class of IOP-lowering drugs, bind to prostaglandin FP receptors in tissues of the uveoscleral pathway. This binding increases the expression of matrix metalloproteinases, which degrade the extracellular matrix of the ciliary body, creating inter-muscular spaces allowing aqueous humor to exit the eye. Drawbacks to prostaglandin F2α analogues include cosmetic side effects, especially prostaglandin-associated periorbitopathy (PAP) syndrome. Areas covered: This review describes the novel prostaglandin E2 receptor antagonist, omidenepag isopropyl, which reduces IOP by improving drainage of uveoscleral and trabecular outflow, increasing the facility of outflow. In contrast to prostaglandin F2α analogues, omidenepag does not inhibit adipogenesis or promote eyelash growth. This review describes preclinical studies of omidenepag, published results of phase I–III clinical trials, and preliminary results of phase III trials currently in progress. Expert opinion: Omidenepag appears to provide IOP reductions comparable to those of prostaglandin F2α analogues, but without the cosmetic side effects common to prostaglandin F2α analogues, especially PAP syndrome. The lack of association between omidenepag and PAP suggests that long-term use of this agent may have advantages in patients with glaucoma.
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    Prostaglandin-Mediated Reinstatement of Drug Taking After Alcohol Drinking by Female Adolescent Rats
    (2022-04) Kline, Hannah L.; Engleman, Eric A.; Atwood, Brady K.; McKinzie, David L.; Truitt, William A.; Yamamoto, Bryan K.
    Adolescent alcohol abuse is a global problem that initiates lifelong addiction. Alcohol use during adolescence is associated with subsequent Meth dependence in humans. Specifically, female adolescents are particularly vulnerable to serial alcohol and Meth use. However, it is unknown if prior voluntary alcohol drinking impacts subsequent Meth-taking in female adolescent rats. Both alcohol and Meth increase the prostaglandin synthesis enzyme cyclooxygenase-2 (COX-2) in the brain but the effect of serial exposure to alcohol and Meth on COX-2 has not been determined. The first study uses a novel method of serial voluntary alcohol drinking and Meth self-administration in female adolescent rats to model human patterns of co-abuse. Prior alcohol drinking did not affect subsequent Meth self-administration, but it reduced the cue-primed reinstatement of Methseeking after abstinence from Meth. Rats with a history of adolescent alcohol drinking also had increased COX-2 in the dorsal striatum, regardless of subsequent Meth selfadministration. These findings demonstrate that a history of adolescent alcohol drinking does not alter Meth self-administration but persistently reduces cue-primed Meth seeking and increases COX-2 after prolonged abstinence from alcohol. To further examine the role of COX-2 in alcohol drinking, the second study found that adolescent alcohol drinking not only increased COX-2 after four weeks of alcohol abstinence, but also increased endothelin-1 (ET-1) and prostaglandin E2 (PGE2) in the dorsal striatum. Furthermore, adolescent alcohol drinking increased alcohol drinking after abstinence, and this increase was attenuated by treatment with the COX-2 inhibitor nimesulide during abstinence. Antagonism of the interaction between PGE2 and its receptor 1 (EP1) also attenuated the increase in relapse drinking and restored alcohol drinking to the rate of alcohol naïve rats. Overall, these experiments identified a prostaglandin-mediated mechanism that is a putative target for the treatment of alcohol relapse following abstinence in individuals with a history of adolescent alcohol abuse.
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    The Antioxidant N-Acetyl Cysteine Inhibits Cytokine and Prostaglandin Release in Human Fetal Membranes Stimulated ex vivo with Lipoteichoic Acid or Live Group B Streptococcus
    (Wiley, 2024) Park, Hae-Ryung; Harris, Sean M.; Boldenow, Erica; Aronoff, David M.; Rea, Meaghan; Xi, Chuanwu; Loch-Caruso, Rita; Medicine, School of Medicine
    Backgrounds: Infection during pregnancy is a significant public health concern due to the increased risk of adverse birth outcomes. Group B Streptococcus or Streptococcus agalactiae (GBS) stands out as a major bacterial cause of neonatal morbidity and mortality. We aimed to explore the involvement of reactive oxygen species (ROS) and oxidative stress pathways in pro-inflammatory responses within human fetal membrane tissue, the target tissue of acute bacterial chorioamnionitis. Methods: We reanalyzed transcriptomic data from fetal membrane explants inoculated with GBS to assess the impact of GBS on oxidative stress and ROS genes/pathways. We conducted pathway enrichment analysis of transcriptomic data using the Database for Annotation, Visualization and Integrated Discovery (DAVID), a web-based functional annotation/pathway enrichment tool. Subsequently, we conducted ex vivo experiments to test the hypothesis that antioxidant treatment could inhibit pathogen-stimulated inflammatory responses in fetal membranes. Results: Using DAVID analysis, we found significant enrichment of pathways related to oxidative stress or ROS in GBS-inoculated human fetal membranes, for example, "Response to Oxidative Stress" (FDR = 0.02) and "Positive Regulation of Reactive Oxygen Species Metabolic Process" (FDR = 2.6*10-4 ). There were 31 significantly changed genes associated with these pathways, most of which were upregulated after GBS inoculation. In ex vivo experiments with choriodecidual membrane explants, our study showed that co-treatment with N-acetylcysteine (NAC) effectively suppressed the release of pro-inflammatory cytokines (IL-6, IL-8, TNF-α) and prostaglandin PGE2, compared to GBS-treated explants (p < .05 compared to GBS-treated samples without NAC co-treatment). Furthermore, NAC treatment inhibited the release of cytokines and PGE2 stimulated by lipoteichoic acid (LTA) and lipopolysaccharide (LPS) in whole membrane explants (p < .05 compared to LTA or LPS-treated samples without NAC co-treatment). Conclusions: Our study sheds light on the potential roles of ROS in governing the innate immune response to GBS infection, offering insights for developing strategies to mitigate GBS-related adverse outcomes.