A citrus flavonoid, 6-demethoxytangeretin, suppresses production and gene expression of interleukin-6 in human mast cell-1 via anaplastic lymphoma kinase and mitogen-activated protein kinase pathways.
Citrus species has been traditionally used in Korea for the treatment of coughing, sputum and dyspepsia. Of the known citrus flavonoids, 6-demethoxytangeretin was reported to exert anti-inflammatory activity. In order to determine the anti-allergic activity of 6-demethoxytangeretin, we examined whether or not 6-demethoxytangeretin was able to suppress activation of the human mast cell line, HMC-1, induced by phorbol 12-myristate 13-acetate (PMA) plus A23187. Interleukin-6 production and relevant gene expression in activated HMC-1 cells were determined by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis. Also, the involvement of the anaplastic lymphoma kinase (ALK) and mitogen-activated protein kinases (MAPKs) in activated HMC-1 cells were studied. 6-Demethoxytangeretin suppresses interleukin-6 production, tumor necrosis factor-alpha gene expression, ALK and MAPKs in HMC-1 cells stimulated by PMA plus A23187. Therefore, it was evident that 6-demethoxytangeretin suppressed activation of HMC-1 cells by PMA plus A23187 by inhibiting the activity of ALK and MAPKs and subsequently suppressing gene expression, which suggest that 6-demethoxytangeretin may be involved in the regulation of mast cell-mediated inflammatory responses.
College of Pharmacy and BK21 PLUS R-FIND Team, Dongguk University-Seoul.
Young-Mi
YM
Kim
Hee-Sung
HS
Chae
Eun Joo
EJ
Lee
Min Hye
MH
Yang
Jin Hee
JH
Park
Kee Dong
KD
Yoon
Jinwoong
J
Kim
Hee Chul
HC
Ahn
Young Hee
YH
Choi
Young-Won
YW
Chin
D000077548:Anaplastic Lymphoma Kinase; D018926:Anti-Allergic Agents / Q000494:pharmacology; D002460:Cell Line; D002957:Citrus; D047309:Flavones / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018926:Anti-Allergic Agents; D047309:Flavones; D005419:Flavonoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C000595792:6-demethoxytangeretin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases