| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Vyas, Vibhuti Ashby, Charles R. Olgun, Nicole S. Sundaram, Sruthi Salami, Oluwabukola Munnangi, Swapna Pekson, Ryan Mahajan, Prathamesh Reznik, Sandra E. |
| Description |
Author Affiliation: Vyas V ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York.); Ashby CR ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York.); Olgun NS ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York); Sundaram S ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York.); Salami O ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York.); Munnangi S ( Emergency Department, Nassau University Medical Center, East Meadow, New York.); Pekson R ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York.); Mahajan P ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York.); Reznik SE ( Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Jamaica, New York) |
| Abstract |
Premature delivery occurs in 12% of all births, and accounts for nearly half of long-term neurological morbidity, and 60% to 80% of perinatal mortality. Despite advances in obstetrics and neonatology, the rate of premature delivery has increased approximately 12% since 1990. The single most common cause of spontaneous preterm birth is infection. Several lines of evidence have demonstrated the role of endothelin-1 as both a constrictor of uterine myometrial smooth muscle and a proinflammatory mediator. Endothelin-1 activates the phospholipase C pathway, leading to activation of protein kinase C and, in turn, sphingosine kinase (SphK). The inhibition of SphK has been recently shown to control the proinflammatory response associated with sepsis. We show herein, for the first time, that SphK inhibition prevents inflammation-associated preterm birth in a murine model. Rescue of pups from premature abortion with an SphK inhibitor occurs by suppression of the proinflammatory cytokines tumor necrosis factor , Il-1ß, and Il-6 and attenuation of polymorphonuclear inflammatory cells into the placental labyrinth. Moreover, we postulate that inhibition of SphK leads to suppression of endothelin-converting enzyme-1 expression, indicating the presence of an endothelin-converting enzyme 1/endothelin 1-SphK positive feedback loop. This work introduces a novel approach for the control of infection-triggered preterm labor, a condition for which there is no effective treatment. |
| File Format |
HTM / HTML |
| ISSN |
00029440 |
| e-ISSN |
15252191 |
| DOI |
10.1016/j.ajpath.2014.10.026 |
| Journal |
The American Journal of Pathology |
| Issue Number |
3 |
| Volume Number |
185 |
| Language |
English |
| Publisher |
Elsevier (on behalf of the American Society for Investigative Pathology) |
| Publisher Date |
2015-03-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Research Support, N.i.h., Extramural Phosphotransferases (alcohol Group Acceptor) Enzyme Inhibitors Premature Birth Cytokines Prevention & Control Discipline Pathology Pharmacology Inflammation Metabolism Drug Effects Therapeutic Use Antagonists & Inhibitors Chemically Induced Lipopolysaccharides Pregnancy Placenta Animals Mice Disease Models, Animal |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Pathology and Forensic Medicine |
