Enhanced production and secretion of glial cell line-derived neurotrophic factor and nerve growth factor from the skin in atopic dermatitis mouse model

Abstract

Role of neurotrophic factors including nerve growth factor (NGF) in the mechanism of overgrowth and hypersensitivity of sensory nerve in atopic dermatitis (AD) has been proposed. Glial cell line-derived neurotrophic factor (GDNF) is a member of neurotrophic factors of the nervous systems; however, the role of GDNF in dermatitis is unknown. IL-18 promotes Th2 type allergic condition in skin and various organs in the absence of IL-12. In this report, we evaluated the expression of GDNF in AD and its association with NGF and IL-18. Mice expressing skin-specific IL-18 (KIL18Tg) or caspase-1, an IL-18 converting enzyme, (KCASP1Tg) were used as AD models; GDNF expression was examined by RT-PCR, enzyme immunoassay, and immunohistochemistry. The mRNA expressions of GDNF and NGF were detected in the epidermis and they were increased in the skin of KIL18Tg and KCASP1Tg mice. GDNF protein production in the skin was also elevated in both transgenic mice and mostly expressed at the basal layer of the epidermis as assessed by immunohistochemistry. Furthermore, the number of nerve fibers was increased in KCASP1Tg, suggesting increased cutaneous innervation. The present results suggest that in addition to NGF, elevated production and secretion of GDNF in the skin associated with overproduction of IL-18 may also be a potent causative factor of itching in AD.