Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor

Title
Chemical allergens stimulate human epidermal keratinocytes to produce lymphangiogenic vascular endothelial growth factor
Author(s)
정태천배옥남[배옥남]안세연[안세연]진선희[진선희]홍수현[홍수현]이진영[이진영]김은선[김은선]천영진[천영진]이애영[이애영]노민수[노민수]
Keywords
CONTACT-DERMATITIS; IN-VITRO; SKIN SENSITIZERS; TNF-ALPHA; LYMPHATIC VESSELS; TRANSGENIC MICE; CELL-LINE; VEGF-C; INFLAMMATION; EXPRESSION
Issue Date
201503
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Citation
TOXICOLOGY AND APPLIED PHARMACOLOGY, v.283, no.2, pp.147 - 155
Abstract
Allergic contact dermatitis (ACD) is a cell-mediated immune response that involves skin sensitization in response to contact with various allergens. Angiogenesis and lymphangiogenesis both play roles in the allergic sensitization process. Epidermal keratinocytes can produce vascular endothelial growth factor (VEGF) in response to UV irradiation and during wound healing. However, the effect of haptenic chemical allergens on the VEGF production of human keratinocytes, which is the primary contact site of toxic allergens, has not been thoroughly researched. We systematically investigated whether immune-regulatory cytokines and chemical allergens would lead to the production of VEGF in normal human keratinocytes (NHKs) in culture. VEGF production significantly increased when NHKs were treated with IFN-gamma, IL-1 alpha, IL-4, IL-6, IL-17A, IL-22 or TNF alpha. Among the human sensitizers listed in the OECD Test Guideline (TG) 429, we found that CMI/MI, DNCB, 4-phenylenediamine, cobalt chloride, 2-mercaptobenzothiazole, citral, HCA, cinnamic alcohol, imidazolidinyl urea and nickel chloride all significantly upregulated VEGF production in NHKs. In addition, common human haptenic allergens such as avobenzone, formaldehyde and urushiol, also induced the keratinocyte-derived VEGF production. VEGF upregulation by pro-inflammatory stimuli, IFN gamma, DNCB or formaldehyde is preceded by the production of IL-8, an acute inflammatory phase cytokine. Lymphangiogenic VEGF-C gene transcription was significantly increased when NHKs were treated with formaldehyde, DNCB or urushiol, while transcription of VEGF-A and VEGF-B did not change. Therefore, the chemical allergen-induced VEGF upregulation is mainly due to the increase in lymphangiogenic VEGF-C transcription in NHKs. These results suggest that keratinocyte-derived VEGF may regulate the lymphangiogenic process during the skin sensitization process of ACD. (C) 2015 Elsevier Inc. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/33108http://dx.doi.org/10.1016/j.taap.2015.01.008
ISSN
0041-008X
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약학대학 > 약학부 > Articles
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