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- Title
(S)-tetrahydroisoquinoline alkaloid inhibits LPS-induced arachidonic acid release through downregulation of cPLA<sub>2</sub> expression.
- Authors
Choi, Jong Min; Choi, Young Hwa; Kim, Seok Kyun; Ahn, Kyong Hoon; Won, Jong Hoon; Lim, Joo Hyuk; Jang, You Jin; Lee, Sungsook; Kim, Dal-Hyun; Kim, Dae Kyong
- Abstract
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 A 2 (cPLA 2) 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 cPLA 2 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 cPLA 2 expression in RAW 264.7 cells.
- Publication
Molecules & Cells (Springer Nature), 2013, Vol 36, Issue 5, p400
- ISSN
1016-8478
- Publication type
Article
- DOI
10.1007/s10059-013-0078-x