title: Luteolin-7-glucoside inhibits IL-22/STAT3 pathway, reducing proliferation, acanthosis, and inflammation in keratinocytes and in mouse psoriatic model.
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 anti-inflammatory 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.
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier, 1, Rome 00133, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Palombo
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier, 1, Rome 00133, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Savini
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier, 1, Rome 00133, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Avigliano
authors.affiliation: Experimental Immunology Laboratory, Biochemistry Laboratory, IDI-IRCCS-FLMM, Via dei Monti di Creta, 104, Rome 00167, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Madonna
authors.affiliation: Experimental Immunology Laboratory, Biochemistry Laboratory, IDI-IRCCS-FLMM, Via dei Monti di Creta, 104, Rome 00167, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Cavani
authors.affiliation: Experimental Immunology Laboratory, Biochemistry Laboratory, IDI-IRCCS-FLMM, Via dei Monti di Creta, 104, Rome 00167, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Albanesi
authors.affiliation: Department Biomedicine and Prevention, University of Rome "Tor Vergata", Via Montpellier, 1, Rome 00133, Italy.
authors.forename: A
authors.identifier: 0000-0002-7351-5676
authors.initials: A
authors.lastname: Mauriello
authors.affiliation: Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier, 1, Rome 00133, Italy.|Medical Research Council, Toxicology Unit, Hodgkin Building, Leicester University, Lancaster Road, P.O. Box 138, Leicester LE1 9HN, UK.
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.affiliation: Biochemistry Laboratory, IDI-IRCCS-FLMM, Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Via Montpellier, 1, Rome 00133, Italy.
authors.forename: A
authors.identifier: 0000-0002-7442-2252
authors.initials: A
authors.lastname: Terrinoni
mesh_terms: D000052:Acanthosis Nigricans / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000634:Aminoquinolines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D004195:Disease Models, Animal; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000077271:Imiquimod; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007378:Interleukins / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008055:Lipids / Q000096:biosynthesis; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects; D010641:Phenotype; D021381:Protein Transport / Q000187:drug effects; D011565:Psoriasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000097043:Interleukin-22
chemical_list: D000634:Aminoquinolines; D005960:Glucosides; D000077271:Imiquimod; D007378:Interleukins; D008055:Lipids; D047311:Luteolin; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C066408:luteolin-7-glucoside