Curcumin inhibits protease-activated receptor-2 and -4-mediated mast cell activation.
BACKGROUND
Curcumin, a major yellow pigment and active component of turmeric powder extracted from Curcuma longa L. (Gingiberaceae), has been shown to possess anti-inflammatory and anti-cancer activities. Protease-activated receptors (PARs) play a role in inflammation, and human leukemic mast cells (HMC-1) co-express PAR2 and PAR4. In the present study, the effect of curcumin on PAR2- and PAR4-mediated HMC-1 activation was examined.


METHODS
HMC-1 cells were stimulated with trypsin (100 nmol/l, PAR2 and PAR4 agonist), SLIGKV-NH(2) (100 microM, PAR2-activating peptide) or GYPGQV-NH(2) (100 micromol/l PAR4-activating peptide) in the presence or absence of curcumin (1, 10, and 100 micromol/l). TNF-alpha secretion was measured by enzyme-linked immunosorbent assay (ELISA). TNF-alpha and tryptase mRNA were measured by reverse-transcription PCR (RT-PCR). Mitogen-activated protein kinase (MAPK) activation was assessed by Western blot analysis. Trypsin activity was measured using the substrate Bz-DL-Arg-p-nitroanilide (BAPNA).


RESULTS
Curcumin (10 and 100 micromol/l) inhibited TNF-alpha secretion from trypsin or activating peptide-stimulated HMC-1. Curcumin (10 and 100 micromol/l) also inhibited TNF-alpha and tryptase mRNA expression in trypsin-stimulated HMC-1. Furthermore, curcumin inhibited trypsin-induced extracellular signal-regulated kinase (ERK) phosphorylation. However, curcumin did not affect the trypsin activity even at 100 micromol/l.


CONCLUSIONS
Curcumin inhibits PAR2- and PAR4-mediated human mast cell activation, not by inhibition of trypsin activity but by block of ERK pathway.
Baek
Ok-Seon
OS
Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, South Korea.
Kang
Ok-Hwa
OH
Choi
Yeon-A
YA
Choi
Suck-Chei
SC
Kim
Tae-Hyun
TH
Nah
Yong-Ho
YH
Kwon
Dong-Yeul
DY
Kim
Yun-Kyung
YK
Kim
Young-Ho
YH
Bae
Ki-Hwan
KH
Lim
Jong-Pil
JP
Lee
Young-Mi
YM
D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics; D014357:Trypsin / Q000378:metabolism; D053802:Tryptases; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D044462:Receptors, Proteinase-Activated; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D012697:Serine Endopeptidases; D014357:Trypsin; D053802:Tryptases; D003474:Curcumin