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Therapeutic effects of heme oxygenase-1 on psoriasiform skin lesions in guinea pigs

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Abstract

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-α 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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Acknowledgments

We thank Hua-Cheng Zhou for his technical assistances, and Chang-Yi Cui for his critical review of the manuscript.

Conflict of interest statement

This paper has no conflicts of interest. We have not a financial relationship with the organization that sponsored the research.

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Authors and Affiliations

  1. Department of Dermatology, Second Affiliated Hospital of Harbin Medical University, 150086, Harbin, Heilongjiang, China

    L. J. Ma, Y. You, B. X. Bai & Yu-Zhen Li

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  1. L. J. Ma
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Correspondence to Yu-Zhen Li.

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Ma, L.J., You, Y., Bai, B.X. et al. Therapeutic effects of heme oxygenase-1 on psoriasiform skin lesions in guinea pigs. Arch Dermatol Res 301, 459–466 (2009). https://doi.org/10.1007/s00403-009-0956-4

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