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A single intradermal injection of IFN-? induces an inflammatory state in both non-lesional psoriatic and healthy skin.

ABSTRACT: Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-? is involved in many cellular processes, including activation of dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-?-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-? was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, which are important contributors to the inflammatory cascade in psoriatic lesions. To determine whether IFN-? indeed induces the pathways expressed in psoriatic lesions, a single intradermal injection of IFN-? was administered to an area of clinically normal, non-lesional (NL) skin of psoriasis patients and biopsies were collected 24 hours later. Although there were no visible changes in the skin, IFN-? induced many molecular and histological features characteristic of psoriatic lesions. IFN-? increased a number of differentially expressed genes in the skin, including many chemokines concomitant with an influx of T cells and inflammatory DCs. Furthermore, inflammatory DC products tumor necrosis factor (TNF), inducible nitric oxide synthase, IL-23, and TNF-related apoptosis-inducing ligand were present in IFN-?-treated skin. Thus, IFN-?, which is significantly elevated in NL skin compared with healthy skin, appears to be a key pathogenic cytokine that can induce many features of the inflammatory cascade of psoriasis.

SUBMITTER: Johnson-Huang LM

PROVIDER: S-EPMC3305841 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin.

Johnson-Huang Leanne M LM Suárez-Fariñas Mayte M Pierson Katherine C KC Fuentes-Duculan Judilyn J Cueto Inna I Lentini Tim T Sullivan-Whalen Mary M Gilleaudeau Patricia P Krueger James G JG Haider Asifa S AS Lowes Michelle A MA

The Journal of investigative dermatology 20120126 4

Psoriasis is a chronic, debilitating, immune-mediated inflammatory skin disease. As IFN-γ is involved in many cellular processes, including activation of dendritic cells (DCs), antigen processing and presentation, cell adhesion and trafficking, and cytokine and chemokine production, IFN-γ-producing Th1 cells were proposed to be integral to the pathogenesis of psoriasis. Recently, IFN-γ was shown to enhance IL-23 and IL-1 production by DCs and subsequently induce Th17 cells, which are important c ...[more]

PMID: 22277938

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Project description:Background: Plaque psoriasis is a chronic autoimmune disorder characterized by the development of red scaly plaques. To date psoriasis lesional skin transcriptome has been extensively studied, whereas only few proteomic studies of psoriatic skin are available. Aim: The aim of this study was to compare protein expression patterns of lesional and normally looking skin of psoriasis patients with skin of the healthy volunteers, reveal differentially expressed proteins and identify changes in cell metabolism caused by the disease. Methods: Skin samples of normally looking and lesional skin donated by psoriasis patients (n = 5) and samples of healthy skin donated by volunteers (n = 5) were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). After protein identification and data processing, the set of differentially expressed proteins was subjected to protein ontology analysis to characterize changes in biological processes, cell components and molecular functions in the patients' skin compared to skin of the healthy volunteers. Results: The performed analysis identified 405 and 59 differentially expressed proteins in lesional and normally looking psoriatic skin compared to healthy control. We discovered decreased expression of KNG1, APOE, HRG, THBS1 and PLG in normally looking skin of the patients. Presumably, these changes were needed to protect the epidermis from spontaneous activation of kallikrein-kinin system and delay the following development of inflammatory response. In lesional skin, we identified several large groups of proteins with coordinated expression. Mainly, these proteins were involved in different aspects of protein and RNA metabolism, namely ATP synthesis and consumption; intracellular trafficking of membrane-bound vesicles, pre-RNA processing, translation, chaperoning and degradation in proteasomes/immunoproteasomes. Conclusion: Our findings explain the molecular basis of metabolic changes caused by disease in skin lesions, such as faster cell turnover and higher metabolic rate. They also indicate on downregulation of kallikrein-kinin system in normally looking skin of the patients that would be needed to delay exacerbation of the disease.

Dataset Information

A single intradermal injection of IFN-? induces an inflammatory state in both non-lesional psoriatic and healthy skin.

Publications

A single intradermal injection of IFN-γ induces an inflammatory state in both non-lesional psoriatic and healthy skin.

Similar Datasets

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