Glutamine inhibits lipopolysaccharide-induced cytoplasmic phospholipase A2 activation and protects against endotoxin shock in mouse.
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 kappaB activation and tumor necrosis factor alpha 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 kappaB/tumor necrosis factor alpha 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.
Department of Immunology, Chonbuk National University Medical School, Jeonju, Korea.
Young-Suk
YS
Kim
Gi-Young
GY
Kim
Jae-Hong
JH
Kim
Hye-Jin
HJ
You
Young-Min
YM
Park
Hern-Ku
HK
Lee
Hee-Chul
HC
Yu
Sung Mo
SM
Chung
Zhe-Wu
ZW
Jin
Hyun-Mi
HM
Ko
Baik-Hwan
BH
Cho
D000818:Animals; D003643:Death; D004195:Disease Models, Animal; D004731:Endotoxins / Q000633:toxicity*; D005973:Glutamine / Q000627:therapeutic use*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005973:Glutamine; D010741:Phospholipases A; D054467:Phospholipases A2