Haem oxygenase-1: a novel player in cutaneous wound repair and psoriasis?

Abstract

Haem oxygenase (HO) is the rate-limiting enzyme in the degradation of haem. In addition to its obvious role in iron metabolism, a series of findings indicate an important role for HO in cellular protection against oxidative stress. This effect might be of particular importance during wound healing and also in inflammatory disease. Therefore we determined the expression of the two HO isoenzymes, HO-1 and HO-2, during the healing process of full-thickness excisional wounds in mice. We show a remarkable induction of HO-1 mRNA and protein expression within three days after skin injury. After completion of wound healing, HO-1 expression declined to basal levels. By contrast, expression of HO-2 was not significantly modulated by skin injury. In situ hybridization and immunohistochemistry revealed high HO-1 expression in inflammatory cells of the granulation tissue and in keratinocytes of the hyperproliferative epithelium. A strong overexpression of HO-1 was also observed in the skin of patients suffering from the inflammatory skin disease psoriasis. In addition, HO-2 mRNA levels were increased in the skin of psoriatic patients. Similar to wounded skin, inflammatory cells and keratinocytes of the hyperthickened epidermis were the major producers of HO-1 in psoriatic skin. In vitro studies with cultured keratinocytes revealed a potential role for reactive oxygen species (ROS), but not for growth factors and pro-inflammatory cytokines, as inducers of HO-1 expression in inflamed skin. Our findings suggest a novel role for HO in wound healing and inflammatory skin disease, where it might be involved in haem degradation and in the protection of cells from the toxic effects of ROS.