The natural flavonoid apigenin suppresses Th1- and Th2-related chemokine production by human monocyte THP-1 cells through mitogen-activated protein kinase pathways.
Dietary flavonoids have various biological functions, and there is increasing evidence that reduced prevalence and severity of allergic reactions are associated with the intake of flavonoids. Among natural flavonoids, apigenin is a potent anti-inflammatory agent. However, the mechanisms of apigenin's effect remain uncertain. Monocyte-derived chemokine (MDC) plays a pivotal role in recruiting T-helper (Th) 2 cells in the allergic inflammation process. In the late phase of allergic inflammation, the Th1 chemokine interferon-inducible protein 10 (IP-10) has also been found in elevated levels in the bronchial alveolar fluid of asthmatic children. We used human THP-1 monocyte cells, pretreated with or without apigenin, prior to lipopolysaccharide stimulation. By means of enzyme-linked immunosorbent assay, we found that apigenin inhibited production of both MDC and IP-10 by THP-1 cells and that the suppressive effect of apigenin was not reversed by the estrogen receptor antagonist ICI182780. The p65 phosphorylation of nuclear factor kappaB remained unaffected, but the phosphorylation of p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase mitogen-activated protein kinase pathways were all blocked. We found that inhibition of c-raf phosphorylation might be the target of apigenin's anti-inflammation property.
Huang
Ching-Hua
CH
Department of Pediatrics, Yuan's General Hospital, Kaohsiung, Taiwan.
Kuo
Po-Lin
PL
Hsu
Ya-Ling
YL
Chang
Tai-Tsung
TT
Tseng
Hsing-I
HI
Chu
Yu-Te
YT
Kuo
Chang-Hung
CH
Chen
Huan-Nan
HN
Hung
Chih-Hsing
CH
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D055745:Bronchioles / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D054357:Chemokine CXCL10 / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004965:Estrogen Antagonists / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000150:complications; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010616:Phenanthrenes; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
C410511:1-keto-1,2,3,4-tetrahydrophenanthrene; D000893:Anti-Inflammatory Agents; D054357:Chemokine CXCL10; D018925:Chemokines; D004965:Estrogen Antagonists; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010616:Phenanthrenes; D010936:Plant Extracts; D011960:Receptors, Estrogen; D047310:Apigenin; D019908:Proto-Oncogene Proteins c-raf; D019892:eIF-2 Kinase; D020928:Mitogen-Activated Protein Kinases