Inhibitory effect of chroman carboxamide on interleukin-6 expression in response to lipopolysaccharide by preventing nuclear factor-κB activation in macrophages

• Published in: European journal of pharmacology Vol. 543; no. 1; pp. 158 - 165
• Main Authors: Hak Kim, Byung, Lee, Kum-Ho, Chung, Eun Yong, Chang, Yoon Sook, Lee, Heesoon, Lee, Chong-Kil, Min, Kyung Rak, Kim, Youngsoo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 14.08.2006; Elsevier
• Subjects: Biological and medical sciences; Chroman carboxamide; Inflammatory cytokine; Interleukin-6; Lipopolysaccharide; Macrophage; Medical sciences; Nuclear factor-κB; Pharmacology. Drug treatments; Lipopolysaccharide; Chroman carboxamide; Inflammatory cytokine; Nuclear factor-κB; Interleukin-6; Macrophage; Chroman derivatives; Interleukin 6; Cytokine; Carboxamide; Transcription factor NFκB
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2006.05.042

6-Hydroxy-7-methoxychroman-2-carboxylic acid (3-nitrophenyl)amide (CP-1158) is a synthetic chroman carboxamide with trolox-like chemical structure. In the present study, CP-1158 was found to inhibit interleukin (IL)-6 production in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7. The CP-1158 attenuated LPS-induced synthesis of IL-6 transcript but also inhibited LPS-induced IL-6 promoter activity. Further, CP-1158 attenuated LPS-induced syntheses of tumor necrosis factor (TNF)-α, IL-1β, interferon-inducible protein (IP)-10 and macrophage inflammatory protein (MIP)-1β transcripts. Nuclear factor (NF)-κB has been evidenced to play a major mechanism in LPS-induced expression of IL-6 or other inflammatory cytokines. CP-1158 prevented LPS-induced nuclear translocation of NF-κB complex and subsequently inhibited DNA binding activity of NF-κB complex as well as NF-κB transcriptional activity in macrophages RAW 264.7. However, CP-1158 did not affect LPS-induced phosphorylation and degradation of inhibitory κB (IκB). In another experiment, CP-1158 inhibited IL-6 promoter activity elicited by expression vectors encoding NF-κB p50 or p65 subunit. Taken together, CP-1158 inhibited LPS-induced expression of inflammatory cytokines including IL-6, targeting NF-κB activating pathway downstream IκB degradation, and thus could provide an anti-inflammatory potential of chroman carboxamide.