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KMID : 0578320130360050400
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Molecules and Cells
2013 Volume.36 No. 5 p.400 ~ p.409
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(S)-Tetrahydroisoquinoline Alkaloid Inhibits LPS-Induced Arachidonic Acid Release through Downregulation of cPLA2 Expression
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Choi Jong-Min
Choi Young-Hwa
Kim Seok-Kyun
Ahn Kyong-Hoon
Won Jong-Hoon
Lim Joo-Hyuk
Jang You-Jin
Lee Sung-Sook
Kim Dal-Hyun
Kim Dae-Kyong
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Abstract
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Sepsis, a systemic inflammatory response syndrome, remains a potentially lethal condition. (S)-1-α-Naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (CKD712) is noted as a drug candidate for sepsis. Many studies have demonstrated its significant anti-inflammatory effects. Here we first examined whether CKD712 inhibits lipopolysaccharide (LPS)-induced arachidonic acid (AA) release in the RAW 264.7 mouse monocyte cell line, and subsequently, its inhibitory mechanisms. CKD712 reversed LPS-associated morphological changes in the RAW 264.7 cells, and inhibited LPS-induced release of AA in a concentrationdependent manner. The inhibition was apparently due to the diminished expression of a cytosolic form of phospholipase A2 (cPLA2) by CKD712, resulting from reduced NF-κB activation. Furthermore, CKD712 inhibited the activation of ERK1/2 and SAP/JNK, but not of p38 MAPK. CKD712 had no effect on the activity or phosphorylation of cPLA2 and on calcium influx. Our results collectively suggest that CKD712 inhibits LPS-induced AA release through the inhibition of a MAPKs/NF-κB pathway leading to reduced cPLA2 expression in RAW 264.7 cells.
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KEYWORD
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CKD712, cPLA2, MAPKs, NF-kappa B, sepsis
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