title: N-(p-Coumaryol)-Tryptamine Suppresses the Activation of JNK/c-Jun Signaling Pathway in LPS-Challenged RAW264.7 Cells.
abstract: N-(p-Coumaryol) tryptamine (CT), a phenolic amide, has been reported to exhibit anti-oxidant and anti-inflammatory activities. However, the underlying mechanism by which CT exerts its pharmacological properties has not been clearly demonstrated. The objective of this study is to elucidate the anti-inflammatory mechanism of CT in lipopolysaccharide (LPS)-challenged RAW264.7 macrophage cells. CT significantly inhibited LPS-induced extracellular secretion of pro-inflammatory mediators such as nitric oxide (NO) and PGE2, and protein expressions of iNOS and COX-2. In addition, CT significantly suppressed LPS-induced secretion of pro-inflammatory cytokines such as TNF-α and IL-1β. To elucidate the underlying anti-inflammatory mechanism of CT, involvement of MAPK and Akt signaling pathways was examined. CT significantly attenuated LPS-induced activation of JNK/c-Jun, but not ERK and p38, in a concentration-dependent manner. Interestingly, CT appeared to suppress LPS-induced Akt phosphorylation. However, JNK inhibition, but not Akt inhibition, resulted in the suppression of LPS-induced responses, suggesting that JNK/c-Jun signaling pathway significantly contributes to LPS-induced inflammatory responses and that LPS-induced Akt phosphorylation might be a compensatory response to a stress condition. Taken together, the present study clearly demonstrates CT exerts anti-inflammatory activity through the suppression of JNK/c-Jun signaling pathway in LPS-challenged RAW264.7 macrophage cells.
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Van Anh
authors.initials: VA
authors.lastname: Vo
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Jun-Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701 ; Department of Radiology, Dongguk University Ilsan Hospital, Ilsan 410-773, Republic of Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon 200-701.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, College of Medicine, Kangwon National University, Chuncheon 200-701.
authors.forename: Wanjoo
authors.initials: W
authors.lastname: Chun
keywords: COX-2; JNK; Lipopolysaccharide; N-(p-Coumaroyl) tryptamine; RAW 264.7 cells; c-Jun; iNOS