Role of corticotropin-releasing hormone and receptor in the pathogenesis of psoriasis

Psoriasis is a chronic inflammatory disease characterized by epidermal keratinocytic hyperproliferation and abnormal differentiation. It is one of the most illustrative examples of the close relation between exacerbation of disease and the psychopathologic burden of the patients. However, the mechanism remains poorly understood. In recent years, evidence has suggested that endocrine stress responses not only are under control of the central nervous system but also occur in peripheral tissue, outside of the classical HPA axis. Corticotrophin-releasing hormone (CRH) is a central component of the hypothalamic-pituitary-adrenal (HPA) axis and is an important coordinator of the systemic stress response. In peripheral sites, cutaneous CRH and CRH-receptor1 (CRH-R1) is believed to regulate various functions of the skin that are important for local homeostasis. These findings have shed new light on the role of peripheral CRH and CRH-R1 in cutaneous diseases, especially psoriasis. Many researchers focus on the pro-inflammatory role of CRH, such as CRH-induced activation of mast cells in the phenomenon of stress related exacerbation of cutaneous inflammatory diseases, and some researches demonstrated that CRH protein expression was increased in the affected skin of psoriasis. Meanwhile, it is reported that CRH could downregulate pro-inflammatory factors, such as IL-18. Tagen found CRH-R1 mRNA expression in psoriasis skin lower than that in normal controls. Previous studies revealed that the functional role of the CRH/CRH-R1 system in pathological human skin conditions remains to be identified. Interestingly, we found that both CRH and CRH-R1 were presented in psoriatic lesion, perilesional skin and normal control skin by immunohistochemistry, and lesions from patients with psoriasis showed significantly lower CRH/CRH-R1 expression compared with psoriatic perilesional skin and normal control skin. Presumably a localized circuit regulates the peripheral functions of cutaneous CRH/CRH-R1, and the aberrant expression of CRH/CRH-R1 in the skin disturbs the local homeostasis and leads to abnormal differentiation and proliferation in keratinocytes. However, dysfunction of keratinocytes may decrease CRH/CRH-R1 expression because of disharmony in differentiation and proliferation of keratinocytes. Thus, we hypothesize that a cutaneous CRH/CRH-R1 system might be aberrant in lesions of psoriasis. The detuning of CRH/CRH-R1 regulation might contribute to the formation of plaque in psoriasis. What is more important, we hypothesize that the role of CRH/CRH-R1 system might play a protective role in the pathogenesis of psoriasis. This would provide a new treatment for psoriasis. Thus, further study in vitro and in vivo has to be done to test our hypothesis. (C) 2009 Elsevier Ltd. All rights reserved.