Possible Role of Heme Oxygenase-1 and Prostaglandins in Pathogenesis of Cerebral Malaria: Induction of Heme Oxygenase-1 by Prostaglandin D2 and Metabolite by Human Astrocyte CCF-STTG1 Cells in Vitro

Abstract

Astrocytes are the most abundant cells in central nervous system that play role in
maintaining the blood-brain-barrier and in neural injury, including cerebral malaria, a severe
complication of Plasmodium falciparum. Prostaglandin DBB2 (BBPGDBB2BB) is abundantly produced in
the brain and regulates the sleep response. Moreover, PGDBB2BB is a potential factor derived from
P.falciparum within erythrocytes. Heme oxygenase-1 (HO-1) is catalyzing enzyme in heme
breakdown process to release iron, carbon monoxide and biliverdin/bilirubin, and may
influence iron supply to the falciparum parasites. Here, we showed that treatment of human
astrocyte cell, CCF-STTG1, with PGDBB2 BBand its metabolite 15d-PGJBB2BB significantly increased
the expression levels of HO-1 mRNA by RT-PCR. Western blot analysis showed that PGDBB2B
and 15d-PGJB2B treatment increased the level of HO-1 protein, in a dose- and time-dependent
manner. Thus, both prostaglandins may be involved in the pathogenesis of cerebral malaria
by inducing HO-1 expression in malaria patients.