Chapter 21 Stimulation of phospholipase A2 expression in rat cultured astrocytes by LPS, TNFα and IL-1β

Abstract

Results from this study are in good agreement with those reported by Oka and Arita (1991) who demonstrated induction of PLA2 mRNA expression in primary astrocytes in response to LPS, TNF alpha and IL-1 beta. In general, the increase in PLA2 mRNA correlated well with the extent of PLA2 secretion into the culture medium. Using the immortalized astrocyte cell line (DITNC), similar induction of PLA2 mRNA expression and secretion of the enzyme into the culture medium could be observed. The lack of hydrolysis of labeled PI to DG further confirmed the specificity of cytokine induction of PLA2 release into the culture medium. By comparing the time course for PLA2 release with that for LDH release, it can be concluded that cytokine induction of PLA2 release is not related to events accompanying cell death due to serum deprivation. Although it has been well demonstrated that exposure of astrocytes to LPS can induce the synthesis and release of TNF alpha and IL-1 beta, the mechanism underlying this event has not been elucidated (Lieberman et al., 1989). Furthermore, how LPS as well as other cytokines induce the mRNA expression and secretion of PLA2 remains to be investigated. The availability of the immortalized astrocyte cell line (DITNC) will be a useful tool for this type of study. These cells are easy to culture and large preparations can be obtained. In addition, these cells will be useful as a model to relate the effects of cytokines on other cellular and metabolic events that may be directly or indirectly linked to the PLA2 cascade.(ABSTRACT TRUNCATED AT 250 WORDS)