The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical antiinflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis

Palombo, R., Savini, I., Avigliano, L., Madonna, S., Cavani, A., Albanesi, C., et al. (2016). Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis and inflammation in keratinocytes and in mouse psoriatic model. CELL DEATH & DISEASE, 7(8) [10.1038/cddis.2016.201].

Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis and inflammation in keratinocytes and in mouse psoriatic model.

PALOMBO, RAMONA;SAVINI, ISABELLA;AVIGLIANO, LUCIANA;MAURIELLO, ALESSANDRO;MELINO, GENNARO;TERRINONI, ALESSANDRO
2016

Abstract

The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical antiinflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
Settore MED/08
Settore BIO/12
English
Con Impact Factor ISI
http://www.nature.com/cddis/journal/v7/n8/full/cddis2016201a.html
Palombo, R., Savini, I., Avigliano, L., Madonna, S., Cavani, A., Albanesi, C., et al. (2016). Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis and inflammation in keratinocytes and in mouse psoriatic model. CELL DEATH & DISEASE, 7(8) [10.1038/cddis.2016.201].
Palombo, R; Savini, I; Avigliano, L; Madonna, S; Cavani, A; Albanesi, C; Mauriello, A; Melino, G; Terrinoni, A
Articolo su rivista
File in questo prodotto:
File Dimensione Formato  
cddis2016201.pdf

accesso aperto

Tipologia: Versione Editoriale (PDF)
Licenza: Copyright dell'editore
Dimensione 4.16 MB
Formato Adobe PDF
4.16 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/177804
Citazioni
  • ???jsp.display-item.citation.pmc??? 29
  • Scopus 61
  • ???jsp.display-item.citation.isi??? 56
social impact