Biological therapy induces expression changes in Notch pathway in psoriasis

Arch Dermatol Res. 2015 Dec;307(10):863-73. doi: 10.1007/s00403-015-1594-7. Epub 2015 Aug 30.

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.

Keywords: Biological therapy; IL-12/IL-23p40; Notch pathway; Psoriasis; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adalimumab / therapeutic use
  • Adult
  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Biological Therapy / methods*
  • Calcium-Binding Proteins / biosynthesis*
  • Calcium-Binding Proteins / genetics
  • Etanercept / therapeutic use
  • Female
  • Homeodomain Proteins / biosynthesis*
  • Homeodomain Proteins / genetics
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Interleukin-12 Subunit p40 / antagonists & inhibitors
  • Jagged-1 Protein
  • Keratinocytes / metabolism
  • Male
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Middle Aged
  • Psoriasis / drug therapy
  • Psoriasis / physiopathology*
  • RNA, Messenger / biosynthesis
  • Receptor, Notch1 / biosynthesis*
  • Receptor, Notch1 / genetics
  • Receptor, Notch2 / biosynthesis*
  • Receptor, Notch2 / genetics
  • Serrate-Jagged Proteins
  • Skin / pathology
  • Transcription Factor HES-1
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Ustekinumab / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Basic Helix-Loop-Helix Transcription Factors
  • Calcium-Binding Proteins
  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-12 Subunit p40
  • JAG1 protein, human
  • Jagged-1 Protein
  • Membrane Proteins
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • RNA, Messenger
  • Receptor, Notch1
  • Receptor, Notch2
  • Serrate-Jagged Proteins
  • Transcription Factor HES-1
  • Tumor Necrosis Factor-alpha
  • HES1 protein, human
  • Ustekinumab
  • Adalimumab
  • Etanercept