Abstract |
Acute or repetitive exposure to ultraviolet (UV) cause disruptions to the skin barrier and subsequent inflammatory skin disease. 4-phenylpyridine (4-PP) is a constituent of Brassica campestris L. ssp. Pekinensis and its effect on skin inflammation and molecular target remain unclear. The purpose of this study is to confirm the anti-inflammatory efficacy of 4-PP on UVB-induced skin inflammation in human keratinocytes HaCaT and mouse skin and validation of its molecular target. 4-PP also attenuated UVB-induced phosphorylation of p38/mitogen-activated protein kinase kinase (MKK) 3/6, c-Jun N-terminal kinase 1/2, MKK 4/7, extracellular-signal-regulated kinase 1/2, mitogen-activated protein kinase 1/2. Additionally, 4-PP inhibited UVB-induced phosphorylation of epidermal growth factor receptor (EGFR) Y1068, Y1045 and 854 residues but not the proto-oncogene tyrosine-protein kinase c-Src. Drug affinity responsive target stability assay revealed that 4-PP directly binds to c-Src and inhibits pronase c-proteolysis. Knockdown of c-Src inhibited UVB-induced COX-2 expression and phosphorylation of MAPKs and EGFR in HaCaT cells. Dorsal treatment of 4-PP prevented UVB (0.5 J/cm2 )-induced skin thickness, phosphorylation of EGFR and COX-2 expression in mouse skin. Our findings suggest that 4-PP can be used as anti-inflammatory agent with an effect of skin inflammation by inhibiting the COX-2 expression via suppressing the c-Src/EGFR/MAPKs signalling pathway.
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Authors | Ju Gyeong Kim, Ha Yeong Kang, Min Jeong Kim, Seokwon Lim, Chang Joo Lee, Kyung-Min Kim, Sung Keun Jung |
Journal | Journal of cellular and molecular medicine
(J Cell Mol Med)
Vol. 26
Issue 14
Pg. 3891-3901
(07 2022)
ISSN: 1582-4934 [Electronic] England |
PMID | 35686492
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. |
Chemical References |
- Pyridines
- 4-phenylpyridine
- Cyclooxygenase 2
- ErbB Receptors
- Protein-Tyrosine Kinases
- Proto-Oncogene Proteins pp60(c-src)
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Topics |
- Animals
- Cyclooxygenase 2
(metabolism)
- Dermatitis
(drug therapy, etiology)
- ErbB Receptors
(metabolism)
- Humans
- Inflammation
(metabolism)
- Keratinocytes
(metabolism)
- Mice
- Phosphorylation
- Protein-Tyrosine Kinases
(metabolism)
- Proto-Oncogene Proteins pp60(c-src)
(metabolism)
- Pyridines
- Skin
(metabolism)
- Ultraviolet Rays
(adverse effects)
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