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(S)-tetrahydroisoquinoline alkaloid inhibits LPS-induced arachidonic acid release through downregulation of cPLA2 expression

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Molecules and Cells

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 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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Authors and Affiliations

  1. Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University, Seoul, 156-756, Korea

    Jong Min Choi, Young Hwa Choi, Seok Kyun Kim, Kyong Hoon Ahn, Jong Hoon Won, Joo Hyuk Lim, You Jin Jang & Dae Kyong Kim

  2. Chong Kun Dang Integrated Research Institute, Cheonan, 331-831, Korea

    Sungsook Lee & Dal-Hyun Kim

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  1. Jong Min Choi
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  2. Young Hwa Choi
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  3. Seok Kyun Kim
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Correspondence to Dae Kyong Kim.

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Choi, J.M., Choi, Y.H., Kim, S.K. et al. (S)-tetrahydroisoquinoline alkaloid inhibits LPS-induced arachidonic acid release through downregulation of cPLA2 expression. Mol Cells 36, 400–409 (2013). https://doi.org/10.1007/s10059-013-0078-x

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