Induction of ferritin and heat shock proteins by prostaglandin A1 in human monocytes. Evidence for transcriptional and post-transcriptional regulation.

Prostaglandins of the A type (PGA) exert a cytoprotective activity during hyperthermia and virus infection. Thiseffect is associated with induction of heat shock proteins (HSP) in mammalian cells. We now report that, inhuman monocytes, PGA1 is able to induce the synthesis of the iron-binding, redox-regulated protein ferritin.L-chain ferritin induction is consequent to a substantial increase in the accumulation of L-chain ferritintranscripts in PGA1-treated cells, whereas H-chain ferritin is regulated post-transcriptionally, consequently toreduction of iron-regulatory protein binding to iron-responsive elements in ferritin mRNA. Ferritin induction isspecific for cyclopentenone prostaglandins (PGA1, PGA2, PGJ2, D12-PGJ2), whereas other arachidonic acid (AA)metabolites have no effect. In human monocytes, PGA1 also induces heat shock gene transcription via heat shockfactor activation, as well as the synthesis of the oxidative-stress protein heme oxygenase (HOS). Differently fromHSP, the induction of ferritin by PGA1 is specific for monocytes. Monocytes/macrophages play a pivotal role ininflammation, controlling iron metabolism and releasing a variety of mediators, including proinflammatoryreactive oxygen species (ROS), cytokines and AA metabolites. As ferritin, together with hsp70 and HO, plays akey role in protection from oxidant damage, these results suggest that PGA1 may have cytoprotective activity alsoduring oxidative injury.