Glutamine Inhibits Lipopolysaccharide-Induced Cytoplasmic Phospholipase A2 Activation and Protects Against Endotoxin Shock in Mouse

This is the authors' abstract. We don't add key points for this paper.

Glutamine (Gln) supplementation is known to play a beneficial role in a number of settings of critical illness as well as laboratory models of endotoxin shock. We have investigated a molecular mechanism of the protective role of Gln in lipopolysaccharide (LPS)-induced shock using a mouse model. To examine the effectiveness of Gln, Gln was administered before or after LPS injection. Treatment of Gln before, but not after, LPS injection resulted in inhibition of nuclear factor κB activation and tumor necrosis factor α synthesis. In contrast, protection of animal from LPS-mediated death by Gln was observed when the Gln treatment was performed after LPS injection, suggesting that nuclear factor κB/tumor necrosis factor α signaling does not play an important role in this process. LPS injection induced phosphorylation of cytoplasmic phospholipase A2 (cPLA2), which was blocked by Gln treatment after LPS injection. Similarly, the LPS-stimulated cPLA2 activity was also inhibited by Gln treatment after LPS injection. Moreover, a cPLA2 inhibitor not only inhibited LPS-induced activation of cPLA2, but also significantly prevented LPS-mediated death. These observations indicate that Gln has a capability to inhibit cPLA2 phosphorylation and activation and suggest that Gln might be of a great therapeutic value for controlling inflammatory diseases in which cPLA2 plays an important role in the pathogenesis of the diseases. ABBREVIATIONS-Gln, glutamine; cPLA2, cytoplasmic phospholipase A2; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κB; TFMK, arachidonyltrifluoromethyl ketone; p65 AS, antisense against p65 components of NF-κB; p65 NS, p65 nonsense against p65 components of NF-κB; TNF-α, tumor necrosis factor α; LPS, lipopolysaccharide; PMSF, phenylmethylsulfonyl fluoride