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.
Ma
L J
LJ
Department of Dermatology, Second Affiliated Hospital of Harbin Medical University, Harbin 150086, Heilongjiang, China.
You
Y
Y
Bai
B X
BX
Li
Yu-Zhen
YZ
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