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The Korean Association of Immunobiologists (대한면역학회)
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CKD-712, (S)-1-(${\alpha}$-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-${\kappa}B$ Activation and Augments Akt Activation during TLR4 Signaling

  • Lee, Jeong-Gi (Department of Microbiology, Brain Korea 21 Project for Medical Science, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine) ;
  • Yang, Eun-Jeong (Department of Microbiology, Brain Korea 21 Project for Medical Science, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine) ;
  • Shin, Jeon-Soo (Department of Microbiology, Brain Korea 21 Project for Medical Science, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine) ;
  • Kim, Dal-Hyun (CKD Research Institute) ;
  • Lee, Sung-Sook (CKD Research Institute) ;
  • Choi, In-Hong (Department of Microbiology, Brain Korea 21 Project for Medical Science, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine)
  • Received : 2011.10.25
  • Accepted : 2011.11.15
  • Published : 2011.12.31
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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-${\kappa}B$ was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-${\kappa}B$ 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-${\kappa}B$ 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.

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References

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