PHOSPHOLIPASE-A2 TRIGGERS THE FIRST-PHASE OF THE THERMAL-STRESS RESPONSE AND EXHIBITS CELL-TYPE SPECIFICITY

To understand the relationship of inflammatory and cellular stress res ponses, phospholipase A(2) (PLA(2)) was examined for its role in the f irst phase of the transcriptional response to cellular stress, Electro mobility shift analysis revealed heat shock transcription factor (HSF1 )-DNA binding when HeLa S3 and Jurkat cells were exposed to exogenous PLA(2). Although PLA(2)-inducible HSF1-DNA binding was comparable to t hermal stress, it did not induce maximal heat shock gene expression, P LA(2)-induced HSF1 was not hyperphosphorylated relative to the heat-in ducible form, thus suggesting that exogenous PLA(2) affects the signal for HSF1 multimerization but not its phosphorylation. Because inflamm ation often involves elevated temperatures, the effect of PLA(2) on th ermal regulation of HSF1-DNA binding activity was examined. PLA(2) exp osure altered the thermal threshold for HSF1 activation, and pore-grad ient gel analysis indicated that either conformational changes or othe r modifications of HSF1 are being induced when cells are treated by PL A(2) thus creating a synergistic environment for HSF1 activation into its DNA-bound state. Surprisingly, the monocyte-like cell line, U-937, was insensitive to the action of exogenous PLA(2). Neither HSF1-DNA b inding or lowering of the temperature threshold for HSF1 activation wa s observed in PLA(2)-treated U-937 cells. These data suggest that infl ammatory mediators such as PLA(2) partially affect transcriptional swi tches mediating thermal stress in some cell types but not others, The purpose of HSF1 activation during inflammation and its differential in duction are discussed relative to these observations.