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Archives of Dermatological Research

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01.11.2015 | Original Paper

Intracellular signaling pathways involved in the release of IL-4 and VEGF from human keratinocytes by activation of kinin B₁ receptor: functional relevance to angiogenesis

verfasst von: Astrid J. Mejia, Carola E. Matus, Francisca Pavicic, Miguel Concha, Pamela Ehrenfeld, Carlos D. Figueroa

Erschienen in: Archives of Dermatological Research | Ausgabe 9/2015

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Abstract

The injured skin produces a number of mediators that directly or indirectly modulate cell chemotaxis, migration, proliferation, and angiogenesis. Components of the kinin pathway including the kinin B₁ receptor (B₁R) have been found to occur in the human skin, but information about its role on keratinocyte biology is still scarce. Our aim was to determine whether stimulation of B₁R causes the secretion of IL-4 and/or VEGF from human keratinocytes and to evaluate the role of the B₁R agonist Lys-des[Arg⁹]bradykinin and IL-4 on various stages of angiogenesis, such as cell migration, proliferation, and release of metalloproteases. By using ELISA and Western blotting, we showed that HaCaT keratinocytes stimulated with the B₁R agonist release IL-4 and VEGF. Stimulation of B₁R also caused transient c-JunN-terminal kinase phosphorylation and JunB nuclear translocation, transcription factor that regulates IL-4 expression. The 3D-angiogenesis assay, performed on spheroids of EA.hy923 endothelial cells embedded in a collagen matrix, showed that their cumulative sprout area increased significantly following stimulation with either IL-4 or B₁R agonist. Furthermore, these ligands produced significant endothelial cell migration and release of metalloproteases 2 and 9, but did not increase endothelial cell proliferation as measured by 5-bromo-2′-deoxyuridine incorporation. Our results provide experimental evidence that establishes IL-4 and B₁R agonist as important angiogenic factors of relevance for skin repair.

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Titel: Intracellular signaling pathways involved in the release of IL-4 and VEGF from human keratinocytes by activation of kinin B1 receptor: functional relevance to angiogenesis
verfasst von: Astrid J. Mejia
Carola E. Matus
Francisca Pavicic
Miguel Concha
Pamela Ehrenfeld
Carlos D. Figueroa
Publikationsdatum: 01.11.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Archives of Dermatological Research / Ausgabe 9/2015
Print ISSN: 0340-3696
Elektronische ISSN: 1432-069X
DOI: https://doi.org/10.1007/s00403-015-1595-6

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