VIA Calcium‐independent phospholipaseA 2 expression after proinflammatory lipopolysaccharide treatment of astrocytes results in augmented Ca 2+ signaling

Many Ca 2+ ‐regulated intracellular processes are involved in the development of neuroinflammation. However, the changes of Ca 2+ signaling in brain under inflammatory conditions were hardly studied. ATP‐induced Ca 2+ signaling is a central event of signal transmission in astrocytic networks. We investigated primary astrocytes after pro‐inflammatory stimulation with lipopolysaccharide. We reveal that Ca 2+ responses to purinergic ATP stimulation are significantly increased in amplitude and duration after stimulation with LPS. We detected that increased amplitudes of Ca 2+ responses to ATP in LPS‐treated astrocytes can be explained by substantial increase of Ca 2+ load in stores in endoplasmic reticulum. The mechanism implies enhanced Ca 2+ store refilling due to the amplification of capacitative Ca 2+ entry. The reason for the increased duration of Ca 2+ responses in LPS‐treated cells is also the amplified capacitative Ca 2+ entry. Next, we established that the molecular mechanism for the LPS‐induced amplification of Ca 2+ responses in astrocytes is increased expression and activity of VIA phospholipase A 2 (VIA iPLA 2 ). Indeed, both gene silencing with specific siRNA and pharmacological inhibition of VIA iPLA 2 with S‐bromoenol lactone reduced the load of the Ca 2+ stores and caused a decrease in the amplitudes of Ca 2+ responses in LPS‐treated astrocytes to values, which were comparable to those in untreated cells. Our findings highlight a novel regulatory role of VIA iPLA 2 in development of inflammation in brain. We suggest that this enzyme might be a possible target for treatment of pathologies related to brain inflammation.