Anti-inflammatory effect of retinoic acid on prostaglandin synthesis in cultured cortical astrocytes

Prostanoids are important mediators of inflammation and pain signaling. Although it is now well accepted that astrocytes participate in inflammatory reactions in the CNS, the molecular regulation of this activity is still largely unknown. Specifically, the regulation of prostanoid synthesis by this type of glia remains to be resolved. Recent evidence suggests that the transcriptional regulator retinoic acid (RA) is involved in regulation of the immune response. We have investigated the expression pattern of the enzymes that catalyze prostanoid and leukotriene synthesis in cultured cortical astrocytes, their stimulation by lipopolysaccharides (LPS) and their regulation by RA. The data indicate that astrocytes are an important source of prostaglandins (PGs) and that RA reduces their inflammatory biosynthesis. LPS treatment induced the expression of enzymes for the production of arachidonic acid and PGs but caused down-regulation of a PG degrading enzyme and of leukotriene synthesizing enzymes that compete with PG synthesis. Consequently, the secretion of the PGE(2) was highly increased after LPS exposure. RA counteracted the inflammatory regulation of cyclooxygenase (COX)-2 mRNA and protein in astrocytes and thereby reduced the synthesis of PGE(2) by approximately 60%. In the absence of LPS, RA enhanced the expression of COX-1 mRNA. In conclusion, RA might be effective in suppressing inflammatory processes in the brain by inhibiting PG synthesis.