Induction of ferritin and heat shock proteins by prostaglandin A(1) in human monocytes - Evidence for transcriptional and post-transcriptional regulation

Prostaglandins of the A type (PGA) exert a cytoprotective activity during h yperthermia and virus infection. This effect is associated with induction o f heat shock proteins (HSP) in mammalian cells. We now report that, in huma n monocytes, PGA(1) is able to induce the synthesis of the iron-binding, re dox-regulated protein -ferritin. L-chain ferritin induction is consequent t o a substantial increase in the accumulation of L-chain ferritin transcript s in PGA(1)-treated cells, whereas H-chain ferritin is regulated post-trans criptionally, consequently to reduction of iron-regulatory protein binding to iron-responsive elements in ferritin mRNA. Ferritin induction is specifi c for cyclopentenone prostaglandins (PGA(1), PGA(2), PGJ(2), Delta(12)-PGJ( 2)), whereas other arachidonic acid (AA) metabolites have no effect. In hum an monocytes, PGA(1) also induces heat shock gene transcription via heat sh ock factor activation, as well as the synthesis of the oxidative-stress pro tein heme oxygenase (HOS). Differently from HSP, the induction of ferritin by PGA(1) is specific for monocytes. Monocytes/macrophages play a pivotal r ole in inflammation, controlling iron metabolism and releasing a variety of mediators, including proinflammatory reactive oxygen species (ROS), cytoki nes and AA metabolites. As ferritin, together with hsp70 and WO, plays a ke y role in protection from oxidant damage, these results suggest that PGA(1) may have cytoprotective activity also during oxidative injury.