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- Title
Intracellular signaling pathways involved in the release of IL-4 and VEGF from human keratinocytes by activation of kinin B receptor: functional relevance to angiogenesis.
- Authors
Mejia, Astrid; Matus, Carola; Pavicic, Francisca; Concha, Miguel; Ehrenfeld, Pamela; Figueroa, Carlos
- 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 B receptor (BR) 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 BR causes the secretion of IL-4 and/or VEGF from human keratinocytes and to evaluate the role of the BR agonist Lys-des[Arg]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 BR agonist release IL-4 and VEGF. Stimulation of BR 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 BR 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 BR agonist as important angiogenic factors of relevance for skin repair.
- Subjects
SKIN wound treatment; NEOVASCULARIZATION; CELL communication; INTERLEUKIN-4; VASCULAR endothelial growth factors; KERATINOCYTES; KININS
- Publication
Archives of Dermatological Research, 2015, Vol 307, Issue 9, p803
- ISSN
0340-3696
- Publication type
Article
- DOI
10.1007/s00403-015-1595-6