|
KMID : 1144820210270040223
|
|
대한의생명과학회지
2021 Volume.27 No. 4 p.223 ~ p.230
|
|
|
Glutamine Inhibits TNF-α-induced Cytosolic Phospholipase A2 Activation via Upregulation of MAPK Phosphatase-1
|
|
Yoon So-Young
Jeong Soo-Yeon
Im Suhn-Young
|
|
|
Abstract
|
|
|
|
Tumor necrosis factor alpha (TNF-α) is a principal regulator of inflammation and immunity. The proinflammatory properties of TNF-α can be attributed to its ability to activate the enzyme cytosolic phospholipase A2 (cPLA2), which generates potent inflammatory lipid mediators, eicosanoids. L-glutamine (Gln) plays physiologically important roles in various metabolic processes. We have reported that Gln has a potent anti-inflammatory activity via rapid upregulation of mitogen-activated protein kinases (MAPKs) phosphatase (MKP)-1, which preferentially dephosphorylates the key proinflammatory enzymes, p38 MAPK and cytosolic phospholipase A2 (cPLA2). In this study, we have investigated whether Gln could inhibit TNF-α-induced cPLA2 activation. Gln inhibited TNF-α-induced increases in cPLA2 phosphorylation in the lungs and blood levels of the cPLA2 metabolites, leukotrine B4 (LTB4) (lipoxygenase metabolite) and prostaglandin E2 (PGE2) (cyclooxygenase metabolite). TNF-α increased p38 and cPLA2 phosphorylation and blood levels of LTB4 and PGE2, which were blocked by the p38 inhibitor SB202190. Gln inhibited TNF-α-induced p38 and cPLA2 phosphorylation and production of the cPLA2 metabolites. Such inhibitory activity of Gln was no longer observed in MKP-1 small interfering RNA-pretreated animals. Our data indicate that Gln inhibited TNF-α-induced cPLA2 phosphorylation through MKP-1 induction/p38 inhibition, and suggest that the utility of Gln in inflammatory diseases in which TNF-α plays a major role in their pathogenesis.
|
|
|
KEYWORD
|
|
|
Glutamine, TNF-α, cPLA2, p38 MAPK, MKP-1
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|