Stabilization of microtubules restores barrier function after cytokine-induced defects in reconstructed human epidermis

Autor: Valérie Pendaries, Nicolas Lecland, Cécile Viodé, Andreas Merdes, Christiane Bierkamp, Carle Paul, Daniel Redoules, Michel Simon, Chiung-Yueh Hsu
Přispěvatelé: Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacochimie Pierre Fabre Dermo-Cosmétique, Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE-PIERRE FABRE, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse]
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Keratinocytes
Intercellular junctions
Paclitaxel
[SDV]Life Sciences [q-bio]
Cell Culture Techniques
Human skin
Dermatology
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Lamellar granule
Filaggrin Proteins
Biochemistry
Microtubules
Dermatitis
Atopic
03 medical and health sciences
chemistry.chemical_compound
Stabilization of microtubules
Microtubule
Cell cortex
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Humans
Molecular Biology
Barrier function
Cells
Cultured
MESH: Cell Culture Techniques Cells
Cultured Cytokines / metabolism Dermatitis
Atopic / drug therapy Dermatitis
Atopic / pathology Epidermal Cells Epidermis / drug effects* Epidermis / pathology Epothilones / pharmacology Epothilones / therapeutic use Humans Keratinocytes / cytology Keratinocytes / drug effects* Keratinocytes / pathology Microtubules / drug effects* Microtubules / pathology Paclitaxel / pharmacology Paclitaxel / therapeutic use Tubulin Modulators / pharmacology* Tubulin Modulators / therapeutic use Water Loss
Insensible / drug effects
Epidermis (botany)
Chemistry
Keratinocyte differentiation
Lamellar bodies
Water Loss
Insensible
Tubulin Modulators
Barrier recovery
Cell biology
Nocodazole
030104 developmental biology
Epidermal Cells
Epothilones
Loricrin
Cytokines
Epidermis
Zdroj: Journal of Dermatological Science
Journal of Dermatological Science, Elsevier, 2018, 91 (1), pp.87-96. ⟨10.1016/j.jdermsci.2018.04.008⟩
ISSN: 0923-1811
DOI: 10.1016/j.jdermsci.2018.04.008⟩
Popis: International audience; Background: A variety of human skin disorders is characterized by defects in the epidermal barrier, leading to dehydration, itchiness, and rashes. Previously published literature suggests that microtubule stabilization at the cortex of differentiating keratinocytes is necessary for the formation of the epidermal barrier. Objectives: We tested whether stabilization of microtubules with paclitaxel or epothilone B can repair barrier defects that were experimentally induced in three-dimensional culture models of epidermis. Methods: We established two models of defective epidermis in vitro, using three-dimensional cultures of primary human keratinocytes on filter supports: immature reconstructed human epidermis (RHE), and RHE that was compromised by treatment with inflammatory cytokines, the latter mimicking defects seen in atopic dermatitis. Results: Both paclitaxel and epothilone B promoted keratinocyte differentiation, accumulation of junctional proteins at the cell cortex, and the early appearance of lamellar bodies in immature RHE, whereas destabilization of microtubules by nocodazole had the reverse effect. Moreover, stabilization of microtubules rescued the barrier after cytokine treatment. The rescued barrier function correlated with the restoration of filaggrin and loricrin protein levels, the cortical accumulation of junctional proteins (E-cadherin, β-catenin, and claudin-1), and with the secretion of lamellar bodies. Conclusions: Our data suggest that the microtubule network is important for the formation of the epidermis, and that stabilization of microtubules promotes barrier formation. Microtubule stabilization may support regeneration of damaged skin, by restoring or improving the barrier.
Databáze: OpenAIRE
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