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The EGFR-ERK/JNK-CCL20 Pathway in Scratched Keratinocytes May Underpin Koebnerization in Psoriasis Patients

Epidermal keratinocytes represent a rich source of C-C motif chemokine 20 (CCL20) and recruit CCR6(+) interleukin (IL)-17A–producing T cells that are known to be pathogenic for psoriasis. A previous study revealed that scratch injury on keratinocytes upregulates CCL20 production, which is implicated...

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Detalles Bibliográficos
Autores principales: Furue, Kazuhisa, Ito, Takamichi, Tanaka, Yuka, Hashimoto-Hachiya, Akiko, Takemura, Masaki, Murata, Maho, Kido-Nakahara, Makiko, Tsuji, Gaku, Nakahara, Takeshi, Furue, Masutaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013594/
https://www.ncbi.nlm.nih.gov/pubmed/31936670
http://dx.doi.org/10.3390/ijms21020434
Descripción
Sumario:Epidermal keratinocytes represent a rich source of C-C motif chemokine 20 (CCL20) and recruit CCR6(+) interleukin (IL)-17A–producing T cells that are known to be pathogenic for psoriasis. A previous study revealed that scratch injury on keratinocytes upregulates CCL20 production, which is implicated in the Koebner phenomenon characteristically seen in psoriasis patients. However, the molecular mechanisms leading to scratch-induced CCL20 production remain elusive. In this study, we demonstrate that scratch injury upregulates the phosphorylation of epidermal growth factor receptor (EGFR) and that the specific EGFR inhibitor PD153035 attenuates scratch-induced CCL20 upregulation in an extracellular signal-related kinase (ERK)-dependent, and to a lesser extent, a c-Jun N-terminal kinase (JNK)-dependent but p38 mitogen-activated protein kinase (MAPK)–independent manner. Immunoreactive CCL20 was visualized in the keratinocytes that lined the scratched wound. IL-17A also induced the phosphorylation of EGFR and further augmented scratch-induced CCL20 upregulation. The EGFR-ERK/JNK-CCL20 pathway in scratched keratinocytes may explain why Koebnerization is frequently seen in psoriasis patients.