Heme oxygenase-1 inhibits cytokine production by activated mast cells.
Heme oxygenase-1 (HO-1) is thought to contribute to host defense reactions against various stresses. In addition, recent reports have suggested that HO-1 modulates immunocyte activation and functions. HO-1 suppresses mast cell degranulation, but whether HO-1 suppresses cytokine synthesis as well is not yet known. We examined whether rat HO-1 cDNA transfected rat basophilic leukemia (RBL)-2H3 cells have altered cytokine production in response to stimulation with anti-ovalbumin (OA) serum/OA compared to Mock transfected RBL-2H3 cells. HO-1 inhibited anti-OA serum/OA-induced IL-3 and TNF-alpha production. Inhibition of HO-1 activity by Zn (II) protoporphyrin IX, a specific HO-1 inhibitor, prevented the suppression of TNF-alpha production. The cytokine inhibition by HO-1 was associated with selective suppression of the DNA-binding activity of AP-1 transcription factors. The suppression of mast cell cytokine production by HO-1 may be an important aspect of the processes that lead to resolution of allergic inflammation.
Yasui
Yumiko
Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihama-bouji, Tokushima-shi, Tokushima 770-8514, Japan. yumikoy@ph.bunri-u.ac.jp
Nakamura
Mao
M
Onda
Toshihiro
T
Uehara
Tomohiro
T
Murata
Saori
S
Matsui
Nobuaki
N
Fukuishi
Nobuyuki
N
Akagi
Reiko
R
Suematsu
Makoto
M
Akagi
Masaaki
M
D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000502:physiology*; D006967:Hypersensitivity / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D008407:Mast Cells / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D018808:Transcription Factor AP-1 / Q000502:physiology
D016207:Cytokines; D018808:Transcription Factor AP-1; D051547:Heme Oxygenase-1