Secreted phospholipase A2 group IIA is a neurotoxin released by stimulated human glial cells

TY - JOUR

T1 - Secreted phospholipase A2 group IIA is a neurotoxin released by stimulated human glial cells

AU - Villanueva, Erika Bianca

AU - Little, Jonathan P

AU - Lambeau, Gerard

AU - Klegeris, Andis

PY - 2012/4

Y1 - 2012/4

N2 - Neuroinflammation, which is one of the hallmarks of neurodegenerative disorders such as Alzheimer's disease, involves secretion of pro-inflammatory mediators by activated glial cells. Secreted phospholipase A 2 group IIA (sPLA 2IIA) has been implicated as an inflammatory mediator contributing to various peripheral inflammatory conditions; however, little is known about the role this enzyme plays in neuroinflammation. Human microglia-like promonocytic THP-1 cells and human primary astrocytes were used to study sPLA 2IIA expression, secretion and function. Production of sPLA 2IIA by these cells was induced in response to stimulation by pro-inflammatory mediators at both mRNA and protein levels. Removal of sPLA 2IIA from stimulated human microglia-like cell and astrocyte supernatants by immunosorbent caused significant reduction of their toxicity towards SH-SY5Y neuroblastoma cells. Both sPLA 2IIA specific and non-specific PLA 2 inhibitors exhibited no anti-cytotoxic or neuroprotective effects, suggesting that sPLA 2IIA cytotoxicity is mediated by a non-enzymatic mechanism. The data obtained indicate that sPLA 2IIA may contribute to the pathogenesis of neurodegenerative diseases involving neuroinflammation. Agents inhibiting the non-enzymatic actions of sPLA 2IIA could be used to slow down progression of neurodegenerative processes that are driven by inflammation.

AB - Neuroinflammation, which is one of the hallmarks of neurodegenerative disorders such as Alzheimer's disease, involves secretion of pro-inflammatory mediators by activated glial cells. Secreted phospholipase A 2 group IIA (sPLA 2IIA) has been implicated as an inflammatory mediator contributing to various peripheral inflammatory conditions; however, little is known about the role this enzyme plays in neuroinflammation. Human microglia-like promonocytic THP-1 cells and human primary astrocytes were used to study sPLA 2IIA expression, secretion and function. Production of sPLA 2IIA by these cells was induced in response to stimulation by pro-inflammatory mediators at both mRNA and protein levels. Removal of sPLA 2IIA from stimulated human microglia-like cell and astrocyte supernatants by immunosorbent caused significant reduction of their toxicity towards SH-SY5Y neuroblastoma cells. Both sPLA 2IIA specific and non-specific PLA 2 inhibitors exhibited no anti-cytotoxic or neuroprotective effects, suggesting that sPLA 2IIA cytotoxicity is mediated by a non-enzymatic mechanism. The data obtained indicate that sPLA 2IIA may contribute to the pathogenesis of neurodegenerative diseases involving neuroinflammation. Agents inhibiting the non-enzymatic actions of sPLA 2IIA could be used to slow down progression of neurodegenerative processes that are driven by inflammation.

U2 - 10.1016/j.mcn.2012.02.006

DO - 10.1016/j.mcn.2012.02.006

M3 - Journal article

SN - 1044-7431

JO - Molecular and Cellular Neuroscience

JF - Molecular and Cellular Neuroscience

ER -