title: CKD-712, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-κB Activation and Augments Akt Activation during TLR4 Signaling.
abstract: Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-κB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-κB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-κB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.
authors.affiliation: Department of Microbiology, Brain Korea 21 Project for Medical Science, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Jeonggi
authors.initials: J
authors.lastname: Lee
authors.forename: Eun-Jeong
authors.initials: EJ
authors.lastname: Yang
authors.forename: Jeon-Soo
authors.initials: JS
authors.lastname: Shin
authors.forename: Dal-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Sung-Sook
authors.initials: SS
authors.lastname: Lee
authors.forename: In-Hong
authors.initials: IH
authors.lastname: Choi