What is a role of haeme oxygenase-1 in psoriasis? Current concepts of pathogenesis.
The skin is constantly exposed to endogenous and environmental pro-oxidant agents, which lead to harmful generation of reactive oxygen species (ROS). Healthy skin, being a potential target for oxidative stress, is equipped with a large number of defence mechanisms including antioxidant systems. This protection can be corrupted by an imbalance between ROS and antioxidants with pathological level of oxidants prevailing. There is a great body of evidence indicating that some inflammatory skin diseases, such as psoriasis, are mediated by oxidative stress. Keratinocytes of normal skin, the primary target for pro-oxidant agents, show strong expression of ROS-detoxifying enzymes. In addition, normal keratinocytes express haeme oxygenase (HO), an enzyme which might be involved in the protection of cells against oxidative stress. HO (inducible HO-1, constitutive HO-2 and HO-3) is the rate-limiting enzyme in haeme catabolism, which leads to the generation of biliverdin, iron, and carbon monoxide. HO-1 is a stress-responsive protein whose expression is induced by various oxidative agents. HO-1 is known for its cytoprotective, antioxidant and anti-inflammatory properties. Interestingly, a strong overexpression of HO-1 was observed in psoriatic skin. However, the role of HO-1 in psoriasis remains unclear. In this review, we will discuss some current concepts concerning pathogenesis of psoriasis and the contribution of HO-1 in skin inflammation to show the relationships between HO-1, ROS and cytokine network in psoriatic skin. We will try to answer a question whether enhanced HO-1 expression in keratinocytes results in beneficial or detrimental effect on the development and severity of psoriatic lesions.
Wojas-Pelc
Anna
A
Department of Dermatology, Jagiellonian University Medical College, Cracow, Poland.
Marcinkiewicz
Janusz
J
D016207:Cytokines / Q000276:immunology; D005293:Ferritins / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology*; D011565:Psoriasis / Q000209:etiology* / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D017382:Reactive Oxygen Species; D005293:Ferritins; D051547:Heme Oxygenase-1