CKD-712, (S)-1-(alpha-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-kappaB Activation and Augments Akt Activation during TLR4 Signaling.
- Author:
Jeonggi LEE
1
;
Eun Jeong YANG
;
Jeon Soo SHIN
;
Dal Hyun KIM
;
Sung Sook LEE
;
In Hong CHOI
Author Information
- Publication Type:Brief Communication
- Keywords: CKD-712; TLR4; Akt; immunomodulator
- MeSH: Blotting, Western; HEK293 Cells; NF-kappa B; Phosphotransferases; Tetrahydroisoquinolines
- From:Immune Network 2011;11(6):420-423
- CountryRepublic of Korea
- Language:English
- 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-kappaB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-kappaB 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-kappaB 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.
