Luteolin 8-C-β-fucopyranoside downregulates IL-6 expression by inhibiting MAPKs and the NF-κB signaling pathway in human monocytic cells.
Numerous studies have been suggested that derivatives can improve the effects of original substances. Therefore, we made luteolin derivative luteolin 8-C-β-fucopyranoside (LU8C-FP) for better anti-inflammatory and anti-cancer effects. In a previous study, we demonstrated that LU8C-FP inhibits invasion of human breast cancer cells via suppression of matrix metalloproteinase 9 and IL-8, which play major roles in tumor progression and cancer cell invasion. Various stimuli trigger inflammatory responses by inducing pro-inflammatory cytokines and chemokines in THP-1 cells. IL-6 induces inflammation via inducing various cytokines and appears to be a potential mediator of inflammatory diseases. Here, we investigated the precise mechanism by which LU8C-FP inhibited phorbol 12-myristate 13-acetate-induced IL-6 mRNA and protein expression. We showed LU8C-FP downregulated IL-6 expression by inhibiting mitogen-activated protein kinases and the nuclear factor-kappaB signaling pathway in human monocytic cells. Furthermore, LU8C-FP exerts less cytotoxicity than luteolin and also it has specific inhibitory effect on IL-6 expression. However, luteolin has a variety of inhibitory effects on pro-inflammatory cytokines and chemokines. Our in vitro studies may provide valuable information leading to the use of LU8C-FP to treat inflammatory diseases caused by IL-6.
Laboratory of Cellular Biology & Immunobiochemistry, Department of Bioscience & Biotechnology, Konkuk University, Seoul, Republic of Korea.
Young Seoung
YS
Lee
Laboratory of Cellular Biology & Immunobiochemistry, Department of Bioscience & Biotechnology, Konkuk University, Seoul, Republic of Korea.
Man Sub
MS
Kim
Laboratory of Cellular Biology & Immunobiochemistry, Department of Bioscience & Biotechnology, Konkuk University, Seoul, Republic of Korea.
Dong Hun
DH
Lee
Laboratory of Cellular Biology & Immunobiochemistry, Department of Bioscience & Biotechnology, Konkuk University, Seoul, Republic of Korea.
Tae Ho
TH
Kwon
Natural Medicine Research Center, Bio-Therapeutics Research Institute, Korea Research Institute of Bioscience & Biotechnology, Cheongwon-gun, Republic of Korea.
Hyuk-Hwan
HH
Song
Natural Medicine Research Center, Bio-Therapeutics Research Institute, Korea Research Institute of Bioscience & Biotechnology, Cheongwon-gun, Republic of Korea.
Sei-Ryang
SR
Oh
Laboratory of Cellular Biology & Immunobiochemistry, Department of Bioscience & Biotechnology, Konkuk University, Seoul, Republic of Korea. Electronic address: ydy4218@konkuk.ac.kr.
Do Young
DY
Yoon
D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
D015850:Interleukin-6; D047311:Luteolin; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D000093242:Interleukin-6 Inhibitors; C508600:IL6 protein, human
IL-6; Inflammation; Luteolin; PMA; THP-1