title: Tetrandrine suppresses pro-inflammatory mediators in PMA plus A23187-induced HMC-1 cells.
abstract: Tetrandrine (TET), a bis-benzylisoquinoline alkaloid from the root of Stephania tetrandra, is known to possess antitumor activity in various malignant neoplasms. However, the precise mechanism of TET-mediated immune modulation remains to be clarified. One of the possible mechanisms for its protective properties is by downregulation of the inflammatory responses. In the present study, the human mast cell line (HMC-1) was used to investigate this effect. TET significantly inhibited the induction of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 by phorbol 12-myristate 13-acetate (PMA) plus A23187. Moreover, TET attenuated expression of cyclooxygenase (COX)-2. In activated HMC-1 cells, the phosphorylation of extra-signal response kinase (ERK1/2) and c-jun N-terminal Kinase (JNK1/2), but not p38 mitogen-activated protein kinase, was decreased by treatment of the cells with TET. TET inhibited PMA plus A23187-induced nuclear factor (NF)-κB activation, IκB degradation and phosphorylation. Furthermore, TET suppressed the expression of TNF-α, IL-8, IL-6 and COX-2 through suppression of the ERK1/2, JNK1/2, IκBα degradation and phosphorylation, and NF-κB activation. These results indicated that TET exerted a regulatory effect on inflammatory reactions mediated by mast cells.
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Wonkwang Oriental Medicines Research Institute, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kang
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Wonkwang Oriental Medicines Research Institute, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Hyeon-Jin
authors.initials: HJ
authors.lastname: An
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.affiliation: BK21 Plus Team, Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Mun
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Wonkwang Oriental Medicines Research Institute, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Yun-Soo
authors.initials: YS
authors.lastname: Seo
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Wonkwang Oriental Medicines Research Institute, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Dae-Ki
authors.initials: DK
authors.lastname: Joung
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Wonkwang Oriental Medicines Research Institute, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Jang-Gi
authors.initials: JG
authors.lastname: Choi
authors.affiliation: Department of Oriental Medicine Resources, Sunchon National University, Sunchon, Jeonnam 540-742, Republic of Korea.
authors.forename: Dong-Won
authors.initials: DW
authors.lastname: Shin
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Wonkwang Oriental Medicines Research Institute, Iksan, Jeonbuk 540-749, Republic of Korea.
authors.forename: Dong-Yeul
authors.initials: DY
authors.lastname: Kwon
mesh_terms: D044182:Benzylisoquinolines / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008407:Mast Cells; D010766:Phosphorylation / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; D015850:Interleukin-6; D016209:Interleukin-8; C009438:tetrandrine; D000001:Calcimycin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate