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.
Keywords:
itch; keratinocyte; nerve growth factor; prurigo nodularis; pruritogenic mediator.
MeSH terms
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Adult
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Cytokines / genetics
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Cytokines / metabolism
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Down-Regulation
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Endothelin-3 / genetics
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Endothelin-3 / metabolism
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Epidermis / metabolism*
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Female
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Gene Expression
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Humans
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Hypersensitivity / complications
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Hypersensitivity / genetics
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Hypersensitivity / metabolism
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Interleukin-7 Receptor alpha Subunit / genetics
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Interleukin-7 Receptor alpha Subunit / metabolism
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Interleukins / genetics
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Interleukins / metabolism
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Keratinocytes / metabolism*
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Male
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Middle Aged
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Nerve Growth Factor / genetics
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Nerve Growth Factor / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Prurigo / complications
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Prurigo / genetics*
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Prurigo / metabolism*
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RNA, Messenger / metabolism
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Receptor, Endothelin B / genetics
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Receptor, Endothelin B / metabolism
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Receptor, trkA / genetics
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Receptor, trkA / metabolism
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Receptors, Cytokine / genetics
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Receptors, Cytokine / metabolism
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Receptors, Interleukin / genetics
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Receptors, Interleukin / metabolism
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Receptors, Nerve Growth Factor / genetics
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Receptors, Nerve Growth Factor / metabolism
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Thymic Stromal Lymphopoietin
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Up-Regulation
Substances
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CRLF2 protein, human
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Cytokines
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EDN3 protein, human
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EDNRB protein, human
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Endothelin-3
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IL31 protein, human
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IL31RA protein, human
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IL7R protein, human
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Interleukin-7 Receptor alpha Subunit
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Interleukins
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NGF protein, human
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NGFR protein, human
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NTRK1 protein, human
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Nerve Tissue Proteins
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RNA, Messenger
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Receptor, Endothelin B
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Receptors, Cytokine
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Receptors, Interleukin
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Receptors, Nerve Growth Factor
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Nerve Growth Factor
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Receptor, trkA
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Thymic Stromal Lymphopoietin