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
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
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje