Heme oxygenase-1 mediates the anti-allergic actions of quercetin in rodent mast cells.
OBJECTIVE
We investigated the involvement of heme oxygenase (HO)-1 in the anti-allergic action of quercetin against degranulation of rat basophilic leukemia (RBL-2H3) cells, rat peritoneal mast cells, and mouse bone marrow-derived mast cells.


METHODS
The strength of allergic reaction was evaluated by the extent of degranulation in mast cells sensitized with various stimulants. The levels of HO-1, HO-2, and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions were determined by quantitative RT-PCR, western blotting, or immunocytochemistry.


RESULTS
Heme oxygenase activity was upregulated after short exposure to quercetin, followed by the induction of HO-1 expression after long exposure to quercetin. The inhibition of degranulation by quercetin was reversed using tin protoporphyrin IX (SnPP), an HO-1 inhibitor. HO-1 metabolites, bilirubin and CO, led to inhibit degranulation, and quercetin translocated Nrf2 from cytoplasm into nucleus in RBL-2H3 cells.


CONCLUSIONS
These results strongly suggest that quercetin exerted anti-allergic actions via activation of Nrf2-HO-1 pathway.
Matsushima
Miyoko
M
MEXT Innovative Research Center for Preventive Medical Engineering, Nagoya University, Furou-cho, Chikusa-ku, Nagoya, 464-8603, Japan.
Takagi
Kenzo
K
Ogawa
Miyuki
M
Hirose
Etsuko
E
Ota
Yui
Y
Abe
Fumie
F
Baba
Kenji
K
Hasegawa
Takaaki
T
Hasegawa
Yoshinori
Y
Kawabe
Tsutomu
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001663:Bilirubin / Q000494:pharmacology; D002248:Carbon Monoxide / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism / Q000473:pathology; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D051267:NF-E2-Related Factor 2; D011524:Protoporphyrins; D002248:Carbon Monoxide; D011794:Quercetin; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D001663:Bilirubin