Acetate Reduces PGE(2) Release and Modulates Phospholipase and Cyclooxygenase Levels in Neuroglia Stimulated with Lipopolysaccharide

作者：Soliman Mahmoud L; Ohm Joyce E; Rosenberger Thad A^*

来源：Lipids, 2013, 48(7): 651-662.

DOI：10.1007/s11745-013-3799-x

• Phospholipase
• Cyclooxygenase
• Eicosanoid
• Acetate
• Histone acetylation

Acetate supplementation attenuates neuroglial activation, increases histone and non-histone protein acetylation, reduces pro-inflammatory cytokine expression, and increases IL-4 transcription in rat models of neuroinflammation and Lyme%26apos;s neuroborreliosis. Because eicosanoid signaling is involved in neuroinflammation, we measured the effect acetate treatment had on phospholipase, cyclooxygenase, and prostaglandin E-2 (PGE(2)) levels in BV-2 microglia and primary astrocytes stimulated with lipopolysaccharide (LPS). In BV-2 microglia, we found that LPS increased the phosphorylation-state of cytosolic phospholipase A(2) (cPLA(2)), reduced the levels of phospholipase C (PLC) beta 1, and increased the levels of cyclooxygenase (Cox)-1 and -2. Acetate treatment returned PLC beta 1 and Cox-1 levels to normal, attenuated the increase in Cox-2, but had no effect on cPLA(2) phosphorylation. In primary astrocytes, LPS increased the phosphorylation of cPLA(2) and increased the levels of Cox-1 and Cox-2. Acetate treatment in these cells reduced secretory PLA(2) IIA and PLC beta 1 levels as compared to LPS-treatment groups, reversed the increase in cPLA(2) phosphorylation, and returned Cox-1 levels to normal. Acetate treatment reduced PGE(2) release in astrocytes stimulated with LPS to control levels, but did not alter PGE(2) levels in BV-2 microglia. The amount of acetylated H3K9 bound to the promoter regions of Cox-1, Cox-2, IL-1 beta and NF-kappa B p65 genes, but not IL-4 in were increased in BV-2 microglia treated with acetate. These data suggest that acetate treatment can disrupt eicosanoid signaling in neuroglia that may, in part, be the result of altering gene expression due chromatin remodeling as a result of increasing H3K9 acetylation.

• 出版日期2013-7