Therapeutic effects of heme oxygenase-1 on psoriasiform skin lesions in guinea pigs.
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.
Department of Dermatology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China.
L J
LJ
Ma
Y
Y
You
B X
BX
Bai
Yu-Zhen
YZ
Li
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006168:Guinea Pigs; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage; D011524:Protoporphyrins / Q000008:administration & dosage; D011565:Psoriasis / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D011524:Protoporphyrins; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C017803:zinc protoporphyrin; C007095:cobaltiprotoporphyrin; D011433:Propranolol; D051547:Heme Oxygenase-1