Prostaglandins of J series control heme oxygenase expression: potential significance in modulating neuroinflammation

Cyclopentenone prostaglandins (cyPGs) are a subfamily of prostaglandins that are characterized by the cyclopentenone ring in their structure. They exert their effect after active transportation into the cell, probably by interacting with cellular target proteins or DNA sequences. The cyPGs have anti-inflammatory activities, especially important during the resolution of inflammation, anticancer, and cytoprotective properties. Here, we show that the cyPGs, especially the 15-deoxy-Delta(12,14) PGJ(2), can specifically induce heme oxygenase 1 in mouse primary neuronal cells. Heme oxygenase is the enzyme responsible for the degradation of heme into biliverdin, ferrous iron, and carbon monoxide. This enzyme conveys protection to oxidative cellular injury by degrading the pro-inflammatory heme; producing biliverdin and bilirubin, potent antioxidants; producing carbon monoxide, a neurotransmitter that also has anti-inflammatory and vasodilatory properties; and assisting in keeping iron cellular homeostasis. CyPGs appear to possess a promising future in designing therapeutics for many neurologic diseases, such as Alzheimer's disease, vascular-related dementia, multiple sclerosis, ischemic conditions, and many others in which inflammation is a part of the pathophysiology.