Content » Vol 99, Issue 6

Investigative Report

Aberrant Expression of Histamine-independent Pruritogenic Mediators in Keratinocytes may be Involved in the Pathogenesis of Prurigo Nodularis

Weilong Zhong, Xia Wu, Wei Zhang, Jie Zhang, Xiaofan Chen, Shihong Chen, Haiyan Huang, Yong Yang, Bo Yu, Xia Dou
DOI: 10.2340/00015555-3150

Abstract

Prurigo nodularis is a highly pruritic and hyperplastic chronic dermatosis with unknown pathogenesis. Many pruritogenic mediators, including nerve growth factor, interleukin (IL)-31, thymic stromal lymphopoietin, and endothelin-1, are implicated in chronic itch and inflammation. This study investigated the mRNA levels and immunoreactivity of the nerve growth factor, IL-31, thymic stromal lymphopoietin, and endothelin axes in both lesional and perilesional skin in prurigo nodularis by using quantitative real-time PCR and immunohistochemistry studies. The nerve growth factor high-affinity receptor tyrosine kinase receptor A was upregulated while the low affinity receptor p75 neurotrophin receptor was downregulated in prurigo nodularis lesions. Downregulated expression of IL-31/IL-31 receptor A and endothelin-3/endothelin receptor B and upregulation of thymic stromal lymphopoietin receptor were found in prurigo nodularis lesions. Aberrant expression of nerve growth factor, IL-31, thymic stromal lymphopoietin and endothelin axes was found in prurigo nodularis lesions, especially in the epidermis, indicating the importance of keratinocytes in prurigo nodularis pathogenesis.

Significance

· Prurigo nodularis is a highly pruritic and hyperplastic chronic dermatosis with studies mainly focusing on cutaneous nerve fibres and neuropeptides. · In this study, aberrant expression of nerve growth factor, interleukin-31, thymic stromal lymphopoietin, and endothelin axes was found in prurigo nodularis lesions, especially in the epidermis, indicating the importance of keratinocytes in prurigo nodularis pathogenesis. · The nerve growth factor high-affinity receptor tyrosine kinase receptor A was upregulated while the low affinity receptor p75 neurotrophin receptor was downregulated in prurigo nodularis lesions, suggesting the importance of receptor imbalance in prurigo nodularis pathogenesis. · These pruritogenic mediators may act as biomarkers for anti-pruritic and anti-inflammatory therapies of prurigo nodularis and need further studies.

Supplementary content

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