Inhibitory effect of chroman carboxamide on interleukin-6 expression in response to lipopolysaccharide by preventing nuclear factor-kappaB activation in macrophages.
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)-alpha, IL-1beta, interferon-inducible protein (IP)-10 and macrophage inflammatory protein (MIP)-1beta transcripts. Nuclear factor (NF)-kappaB 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-kappaB complex and subsequently inhibited DNA binding activity of NF-kappaB complex as well as NF-kappaB transcriptional activity in macrophages RAW 264.7. However, CP-1158 did not affect LPS-induced phosphorylation and degradation of inhibitory kappaB (IkappaB). In another experiment, CP-1158 inhibited IL-6 promoter activity elicited by expression vectors encoding NF-kappaB p50 or p65 subunit. Taken together, CP-1158 inhibited LPS-induced expression of inflammatory cytokines including IL-6, targeting NF-kappaB activating pathway downstream IkappaB degradation, and thus could provide an anti-inflammatory potential of chroman carboxamide.
Kim
Byung Hak
BH
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Korea.
Lee
Kum-Ho
KH
Chung
Eun Yong
EY
Chang
Yoon Sook
YS
Lee
Heesoon
H
Lee
Chong-Kil
CK
Min
Kyung Rak
KR
Kim
Youngsoo
Y
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism; D002839:Chromans / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005822:Genetic Vectors; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D009574:Nitro Compounds / Q000494:pharmacology*; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
C515245:6-hydroxy-7-methoxychroman-2-carboxylic acid (3-nitrophenyl)amide; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D002839:Chromans; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C000606205:Nfkbia protein, mouse; D009574:Nitro Compounds; D012333:RNA, Messenger; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C073701:Nfkb1 protein, mouse; D004247:DNA