Induction of Cytosolic Phospholipase A2 mRNA Expression by Interleukin-1β and Tumor Necrosis Factor α in Human Gingival Fibroblasts

Abstract

The involvement of phospholipase A2 (PLA2) enzymes, the 85 kDa cytosolic PLA2 (cPLA2) and the 14 kDa secretory PLA2 (sPLA2), on PGE2 production in human gingival fibroblasts was investigated. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the inflammatory mediators interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) induce the mRNA expression of cPLA2 in gingival fibroblasts. In addition, treatment of the cells with calcium ionophore, A23187, or the protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA), also induced cPLA2 mRNA expression, accompanied by enhanced PGE2 production. The anti-inflammatory steroid dexamethasone (DEX) reduced basal cPLA2 mRNA expression as well as blocked the induction of cPLA2 mRNA by IL-1β and TNFα in gingival fibroblasts. In contrast to cPLA2, the expression of sPLA2 mRNA was not detected either in untreated or in treated gingival fibroblasts. The study demonstrates that cPLA2 mRNA expression is upregulated by IL-1β and TNFα in human gingival fibroblasts suggesting an important role for the enzyme cPLA2 in the cytokine-induced PGE2 production. Furthermore, the enzyme cPLA2, rather than sPLA2, may be involved in the pathogenesis of periodontal disease by mediating PGE2 production in gingival fibroblasts.