Dual Inhibition of PI3K/Akt and mTOR by ...
Type de document :
Article dans une revue scientifique
DOI :
PMID :
URL permanente :
Titre :
Dual Inhibition of PI3K/Akt and mTOR by the Dietary Antioxidant, Delphinidin, Ameliorates Psoriatic Features In Vitro and in an Imiquimod-Induced Psoriasis-Like Disease in Mice.
Auteur(s) :
Chamcheu, Jean Christopher [Auteur]
Adhami, Vaqar M [Auteur]
Esnault, Stephane [Auteur]
Sechi, Mario [Auteur]
Siddiqui, Imtiaz A [Auteur]
Satyshur, Kenneth A [Auteur]
Syed, Deeba N [Auteur]
Dodwad, Shah-Jahan M [Auteur]
Chaves-Rodriquez, Maria-Ines [Auteur]
Longley, B Jack [Auteur]
Wood, Gary S [Auteur]
Mukhtar, Hasan [Auteur]
Adhami, Vaqar M [Auteur]
Esnault, Stephane [Auteur]
Sechi, Mario [Auteur]
Siddiqui, Imtiaz A [Auteur]
Satyshur, Kenneth A [Auteur]
Syed, Deeba N [Auteur]
Dodwad, Shah-Jahan M [Auteur]
Chaves-Rodriquez, Maria-Ines [Auteur]
Longley, B Jack [Auteur]
Wood, Gary S [Auteur]
Mukhtar, Hasan [Auteur]
Titre de la revue :
Antioxidants & redox signaling
Nom court de la revue :
Antioxid Redox Signal
Numéro :
26
Pagination :
49-69
Date de publication :
2017-01-10
ISSN :
1557-7716
Mot(s)-clé(s) en anglais :
Administration, Topical
Aminoquinolines
Animals
Anthocyanins
Antioxidants
Binding Sites
Biopsy
Chemotaxis, Leukocyte
Cytokines
Disease Models, Animal
Imiquimod
Immunomodulation
Inflammation Mediators
Mice
Models, Molecular
Molecular Conformation
Neutrophils
Phosphatidylinositol 3-Kinases
Phosphoinositide-3 Kinase Inhibitors
Protein Binding
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-akt
Psoriasis
Ribosomal Protein S6 Kinases, 70-kDa
Signal Transduction
Skin
TOR Serine-Threonine Kinases
antioxidants
delphinidin
imiquimod model of inflammation
psoriasis
Aminoquinolines
Animals
Anthocyanins
Antioxidants
Binding Sites
Biopsy
Chemotaxis, Leukocyte
Cytokines
Disease Models, Animal
Imiquimod
Immunomodulation
Inflammation Mediators
Mice
Models, Molecular
Molecular Conformation
Neutrophils
Phosphatidylinositol 3-Kinases
Phosphoinositide-3 Kinase Inhibitors
Protein Binding
Protein Kinase Inhibitors
Proto-Oncogene Proteins c-akt
Psoriasis
Ribosomal Protein S6 Kinases, 70-kDa
Signal Transduction
Skin
TOR Serine-Threonine Kinases
antioxidants
delphinidin
imiquimod model of inflammation
psoriasis
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
The treatment of psoriasis remains elusive, underscoring the need for identifying novel disease targets and mechanism-based therapeutic approaches. We recently reported that the PI3K/Akt/mTOR pathway that is frequently ...
Lire la suite >The treatment of psoriasis remains elusive, underscoring the need for identifying novel disease targets and mechanism-based therapeutic approaches. We recently reported that the PI3K/Akt/mTOR pathway that is frequently deregulated in many malignancies is also clinically relevant for psoriasis. We also provided rationale for developing delphinidin (Del), a dietary antioxidant for the management of psoriasis. This study utilized high-throughput biophysical and biochemical approaches and in vitro and in vivo models to identify molecular targets regulated by Del in psoriasis. A kinome-level screen and Kds analyses against a panel of 102 human kinase targets showed that Del binds to three lipid (PIK3CG, PIK3C2B, and PIK3CA) and six serine/threonine (PIM1, PIM3, mTOR, S6K1, PLK2, and AURKB) kinases, five of which belong to the PI3K/Akt/mTOR pathway. Surface plasmon resonance and in silico molecular modeling corroborated Del's direct interactions with three PI3Ks (α/c2β/γ), mTOR, and p70S6K. Del treatment of interleukin-22 or TPA-stimulated normal human epidermal keratinocytes (NHEKs) significantly inhibited proliferation, activation of PI3K/Akt/mTOR components, and secretion of proinflammatory cytokines and chemokines. To establish the in vivo relevance of these findings, an imiquimod (IMQ)-induced Balb/c mouse psoriasis-like skin model was employed. Topical treatment of Del significantly decreased (i) hyperproliferation and epidermal thickness, (ii) skin infiltration by immune cells, (iii) psoriasis-related cytokines/chemokines, (iv) PI3K/Akt/mTOR pathway activation, and (v) increased differentiation when compared with controls. Innovation and Conclusion: Our observation that Del inhibits key kinases involved in psoriasis pathogenesis and alleviates IMQ-induced murine psoriasis-like disease suggests a novel PI3K/AKT/mTOR pathway modulator that could be developed to treat psoriasis. Antioxid. Redox Signal. 26, 49-69.Lire moins >
Lire la suite >The treatment of psoriasis remains elusive, underscoring the need for identifying novel disease targets and mechanism-based therapeutic approaches. We recently reported that the PI3K/Akt/mTOR pathway that is frequently deregulated in many malignancies is also clinically relevant for psoriasis. We also provided rationale for developing delphinidin (Del), a dietary antioxidant for the management of psoriasis. This study utilized high-throughput biophysical and biochemical approaches and in vitro and in vivo models to identify molecular targets regulated by Del in psoriasis. A kinome-level screen and Kds analyses against a panel of 102 human kinase targets showed that Del binds to three lipid (PIK3CG, PIK3C2B, and PIK3CA) and six serine/threonine (PIM1, PIM3, mTOR, S6K1, PLK2, and AURKB) kinases, five of which belong to the PI3K/Akt/mTOR pathway. Surface plasmon resonance and in silico molecular modeling corroborated Del's direct interactions with three PI3Ks (α/c2β/γ), mTOR, and p70S6K. Del treatment of interleukin-22 or TPA-stimulated normal human epidermal keratinocytes (NHEKs) significantly inhibited proliferation, activation of PI3K/Akt/mTOR components, and secretion of proinflammatory cytokines and chemokines. To establish the in vivo relevance of these findings, an imiquimod (IMQ)-induced Balb/c mouse psoriasis-like skin model was employed. Topical treatment of Del significantly decreased (i) hyperproliferation and epidermal thickness, (ii) skin infiltration by immune cells, (iii) psoriasis-related cytokines/chemokines, (iv) PI3K/Akt/mTOR pathway activation, and (v) increased differentiation when compared with controls. Innovation and Conclusion: Our observation that Del inhibits key kinases involved in psoriasis pathogenesis and alleviates IMQ-induced murine psoriasis-like disease suggests a novel PI3K/AKT/mTOR pathway modulator that could be developed to treat psoriasis. Antioxid. Redox Signal. 26, 49-69.Lire moins >
Langue :
Anglais
Comité de lecture :
Oui
Audience :
Non spécifiée
Établissement(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Collections :
Date de dépôt :
2023-10-23T15:16:55Z
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