title: Biological therapy induces expression changes in Notch pathway in psoriasis.
abstract: Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.
authors: Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.
authors: Evangelia
authors: E
authors: Skarmoutsou
authors: Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.
authors: Chiara
authors: C
authors: Trovato
authors: Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.
authors: Mariagrazia
authors: M
authors: Granata
authors: Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.
authors: Giulio A
authors: GA
authors: Rossi
authors: Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.
authors: Ambra
authors: A
authors: Mosca
authors: Unità Operativa Complessa di Dermatologia, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, Catania, Italy.
authors: Valentina
authors: V
authors: Longo
authors: Servizio di Anatomia Patologica, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, Catania, Italy.
authors: Pietro
authors: P
authors: Gangemi
authors: Unità Operativa Complessa di Dermatologia, Azienda Ospedaliera Universitaria Policlinico-Vittorio Emanuele, Catania, Italy.
authors: Maurizio
authors: M
authors: Pettinato
authors: Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy. f.damico@unict.it.
authors: Fabio
authors: F
authors: D'Amico
authors: Department of Biomedical and Biotechnological Sciences, University of Catania, via Androne 83, 95124, Catania, Italy.
authors: Maria Clorinda
authors: MC
authors: Mazzarino
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D001691:Biological Therapy / Q000379:methods*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D000068800:Etanercept / Q000627:therapeutic use; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D053762:Interleukin-12 Subunit p40 / Q000037:antagonists & inhibitors; D000072100:Jagged-1 Protein; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051881:Receptor, Notch1 / Q000096:biosynthesis* / Q000235:genetics; D051883:Receptor, Notch2 / Q000096:biosynthesis* / Q000235:genetics; D000072099:Serrate-Jagged Proteins; D012867:Skin / Q000473:pathology; D000072056:Transcription Factor HES-1; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000069549:Ustekinumab / Q000627:therapeutic use
chemical_list: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D000068800:Etanercept; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D053762:Interleukin-12 Subunit p40; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000072099:Serrate-Jagged Proteins; D000072056:Transcription Factor HES-1; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab; C000606273:JAG1 protein, human; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; C078493:HES1 protein, human
keywords: Biological therapy; IL-12/IL-23p40; Notch pathway; Psoriasis; TNF-α