The Glycogen Synthase Kinase 3a and b Isoforms Differentially Regulates Interleukin-12p40 Expression in Endothelial Cells Stimulated with Peptidoglycan from XXXX .

@entity32 @entity20134 @entity6 @entity146 @entity5 @entity794 @entity46343 @entity214 @entity25650 @entity291 @entity65 @entity71562 @entity47143
Glycogen synthase kinase 3 (GSK3) is a constitutively active regulatory enzyme that is important in @entity5 , @entity6 , and @entity65 . While @entity71562 is usually important in neurodegenerative and @entity146 @entity46343 is fundamental in the inflammatory response caused by bacterial components. Peptidoglycan (PGN), one of the most abundant cell-wall structures of Gram-positive bacteria, is an important inducer of @entity32 . To evaluate whether inhibition of @entity71562 and @entity46343 activity in @entity291 endothelial cells (BEC) regulates the expression of the pro-inflammatory cytokine @entity47143 , we treated BEC with @entity214 -purified PGN from @entity794 . We found that PGN triggered a TLR2/PI3K/Akt-dependent phosphorylation of @entity71562 at Ser21, @entity46343 at Ser9, and NF-kB p65 subunit (p65) at Ser536, and the phosphorylation of @entity71562 was consistently higher than that of @entity46343 . The expression of @entity47143 was inhibited in BEC stimulated with PGN and pre-treated with a specific neutralizing anti-TLR2 antibody that targets the extracellular domain of TLR2 or by the addition of Akt-i IV (an Akt inhibitor). Inhibition of @entity71562 and @entity46343 with @entity20134 or @entity25650 induced an increase in @entity47143 mRNA and protein. The effect of each isoform on @entity47143 expression was evaluated by siRNA-gene expression silencing of @entity71562 and @entity46343 . @entity71562 gene silencing resulted in a marked increase in @entity47143 mRNA and protein while @entity46343 gene silencing had the opposite effect on @entity47143 expression. These results indicate that the TLR2/PI3K/Akt-dependent inhibition of @entity71562 activity also plays an important role in the inflammatory response caused by stimulation of BEC with PGN from @entity794 .
