期刊
ARCHIVES OF DERMATOLOGICAL RESEARCH
卷 301, 期 6, 页码 459-466出版社
SPRINGER
DOI: 10.1007/s00403-009-0956-4
关键词
Heme oxygenase-1 (HO-1); Psoriasiform; Propranolol; In vivo; Animal model
类别
Heme oxygenase-1 (HO-1) has been shown to exert immunosuppressive, anti-inflammatory, anti-apoptotic and anti-proliferative effects. Its unique positive effects indicate that this enzyme might be a potential therapeutic target for psoriasis. To determine the effect of pharmacologic up-regulation of HO-1 on psoriasis, we generated a guinea pig model of psoriasiform skin lesions using propranolol induction. In this in vivo model, the 3-week propranolol challenge generated the psoriasiform pathological changes on the ears of guinea pigs. And then, guinea pigs were intraperitoneally injected with 5 mg/kg cobalt protoporphyrin (CoPP), a potent HO-1 inducer, 20 mg/kg zinc protoporphyrin, an inhibitor of HO-1, or PBS as controls, once a week from 9 weeks of age to 14 weeks old. CoPP induced notably HO-1 expression at both mRNA and protein levels. Moreover, CoPP treatment led to a significant reduction of the psoriasiform histopathological changes and remarkable amelioration of the psoriasiform skin lesions, compared with PBS treatment, with a concomitant reduction in proliferating cell nuclear antigen expression. Additionally, CoPP treatment resulted in a decreased TNF-alpha and significantly increased IL-10 release. Our results suggest that HO-1 induction therapy ameliorates the psoriasiform skin lesions by suppressing keratinocyte hyperproliferation and attenuating production of inflammatory responses.
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