Interleukin (IL)-17/IL-36 axis participates to the crosstalk between endothelial cells and keratinocytes during inflammatory skin responses
Autor: | Stefania Rossi, Francesco Facchiano, Lorena Capriotti, Cristina Maria Failla, Gianluca Pagnanelli, Claudia Scarponi, Laura Mercurio, Andrea Cavani, Martina Morelli, Cristina Albanesi, Stefania Madonna |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Keratinocytes
Vascular Endothelial Growth Factor A 0301 basic medicine Chemokine Physiology medicine.medical_treatment Cell Communication Pathology and Laboratory Medicine Epithelium 0302 clinical medicine Animal Cells Immune Physiology Medicine and Health Sciences Receptor Immune Response Cells Cultured Mitogen-Activated Protein Kinase 1 Innate Immune System Mitogen-Activated Protein Kinase 3 Multidisciplinary biology integumentary system Cell adhesion molecule Chemistry Interleukin-17 NF-kappa B Interleukin Animal Models Intercellular Adhesion Molecule-1 Endothelial stem cell Cytokine Experimental Organism Systems Cell Processes 030220 oncology & carcinogenesis Cytokines Medicine Tumor necrosis factor alpha Interleukin 17 Cellular Types Anatomy medicine.symptom Research Article STAT3 Transcription Factor Adhesion Molecules Science Immunology Mouse Models Inflammation Research and Analysis Methods Autoimmune Diseases Proinflammatory cytokine 03 medical and health sciences Signs and Symptoms Model Organisms Diagnostic Medicine medicine Psoriasis Humans Cell Proliferation Biology and Life Sciences Endothelial Cells Epithelial Cells Cell Biology Molecular Development Biological Tissue 030104 developmental biology Immune System Animal Studies biology.protein Cancer research Clinical Immunology Clinical Medicine Developmental Biology Interleukin-1 |
Zdroj: | PLoS ONE, Vol 15, Iss 4, p e0222969 (2020) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | In inflammatory skin conditions, such as psoriasis, vascular enlargement is associated with endothelial cell proliferation, release of cytokines and adhesion molecule expression. Interleukin (IL)-17A is a pro-inflammatory cytokine mainly secreted by T helper-17 cells that is critically involved in psoriasis pathogenesis. IL-36α, IL-36β and IL-36γ are also inflammatory cytokines up-regulated in psoriasis and induced by various stimuli, including IL-17A. In this study, we found that human keratinocytes are the main source of IL-36, in particular of IL-36γ. This cytokine was strongly induced by IL-17A and, together with IL-17A, efficiently activated human dermal microvascular endothelial cells (HDMECs), which expressed both IL-17 and IL-36 receptors. Both IL-36γ and IL-17A induced cell proliferation through specific molecular cascades involving ERK1/2 only or ERK1/2, STAT3 and NF-κB, respectively. We highlighted the intense IL-17A- and IL-36γ -dependent interplay between keratinocytes and HDMECs, likely active in the psoriatic lesions and leading to the establishment of a cytokine network responsible for the development and maintenance of the inflamed state. IL-17A or IL-36γ showed in HDMECs a synergic activity with TNF-α by potently inducing inflammatory cytokine/chemokine release and ICAM-1 expression. We also investigated the involvement of IL-36γ and VEGF-A, substantially reduced in lesional skin of psoriatic patients pharmacologically treated with the anti-IL-17A antibody Secukinumab. Importantly, keratinocyte-derived IL-36γ represented an additional pro-angiogenic mediator of IL-17A. We observed that keratinocyte-derived VEGF-A influenced proliferation but did not act on expression of adhesion molecules in HDMECs. On the other hand, inhibition of IL-36γ released by IL-17A-treated keratinocytes impaired either proliferation or ICAM-1 expression both in HDMECs and in an in vivo murine model of psoriasis. Taken together, our data demonstrated that IL-17A and IL-36γ are highly involved in endothelial cells/keratinocytes crosstalk in inflammatory skin conditions. |
Databáze: | OpenAIRE |
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