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The psoriatic shift induced by interleukin 17 is promptly reverted by a specific anti-IL-17A agent in a three-dimensional organotypic model of normal human skin culture
- Source :
- European Journal of Histochemistry : EJH, European Journal of Histochemistry, Vol 64, Iss 2 (2020)
- Publication Year :
- 2020
- Publisher :
- PAGEPress Publications, Pavia, Italy, 2020.
-
Abstract
- Interleukin 17A (IL-17A), mainly produced by the T helper subclass Th17, plays a key role in the psoriatic plaque formation and progression. The clinical effectiveness of anti-IL-17A agents is documented, but the early and specific mechanisms of their protection are not identified yet. The challenge of the present study is to investigate the possible reversal exerted by a specific anti-IL-17A agent on the psoriatic events induced by IL-17A in a three-dimensional organotypic model of normal human skin. Bioptic skin fragments obtained after aesthetic surgery of healthy women (n=5) were incubated with i) IL-17A biological inhibitor (anti-IL-17A), ii) IL-17A, iii) a combination of IL-17A and its specific IL-17A biological inhibitor (COMBO). A Control group was in parallel cultured and incubation lasted for 24 and 48 h epidermal-side-up at the air-liquid interface. All subjects were represented in all experimental groups at all considered time-points. Keratinocyte proliferation and the presence of epidermal Langerhans cells were quantitatively estimated. In parallel with transmission electron microscopy analysis, immunofluorescence studies for the epidermal distribution of keratin (K)10, K14, K16, K17, filaggrin/occludin, Toll-like Receptor 4, and Nuclear Factor kB were performed. IL-17A inhibited cell proliferation and induced K17 expression, while samples incubated with the anti-IL-17A agent were comparable to controls. In the COMBO group the IL-17A-induced effects were almost completely reverted. Our study, for the first time, elucidates the most specific psoriatic cellular events that can be partially affected or completely reverted by a specific anti-IL-17A agent during the early phases of the plaque onset and progression. On the whole, this work contributes to expand the knowledge of the psoriatic tableau.
- Subjects :
- 0301 basic medicine
keratinocytes
Adult
Histology
keratin 17
Biophysics
Human skin
Filaggrin Proteins
Immunofluorescence
Occludin
Keratin 17
Article
03 medical and health sciences
Young Adult
0302 clinical medicine
Keratin
transmission electron microscopy
medicine
Humans
Psoriasis
lcsh:QH301-705.5
Skin
chemistry.chemical_classification
medicine.diagnostic_test
integumentary system
epidermal barrier
Interleukin-17
S100 Proteins
Antibodies, Monoclonal
NF-kappa B p50 Subunit
Cell Biology
Molecular biology
Toll-Like Receptor 4
030104 developmental biology
medicine.anatomical_structure
cell proliferation
lcsh:Biology (General)
chemistry
030220 oncology & carcinogenesis
Langerhans Cells
Keratins
Female
Interleukin 17
Keratinocyte
Filaggrin
Subjects
Details
- Language :
- English
- ISSN :
- 20388306 and 1121760X
- Volume :
- 64
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- European Journal of Histochemistry : EJH
- Accession number :
- edsair.doi.dedup.....0896e74f8fbc31e93fc16a45092b1d39