ABSTRACT
Psoriasis is a chronic inflammatory skin disease with a prevalence of 2-3 %. It appears to result from a combination of genetic and environmental factors, but the precise pathogenesis is still unknown. Neurogenic inflammation is involved in psoriasis pathogenesis as well, but the role of neurogenic factors is currently unclear. Molecular studies often involve material obtained from patients. However, many questions and especially experimental manipulations are not suited for study in humans. Imiquimod application on mouse skin leads to immune cell infiltration, inflammation with intense redness, epidermal thickening, and scaling that jointly greatly resembles human psoriasis. Here we describe the use of surgical denervation in the imiquimod-induced psoriasiform model, to study the role of skin innervation and neuropeptides in the pathogenesis of psoriasis.
Subject(s)
Denervation/methods , Dermatologic Surgical Procedures/methods , Psoriasis/immunology , Skin/drug effects , T-Lymphocytes/drug effects , Aminoquinolines/adverse effects , Animals , Denervation/instrumentation , Dermatologic Surgical Procedures/instrumentation , Disease Models, Animal , Female , Gene Expression Regulation , Humans , Imiquimod , Interleukin-17/genetics , Interleukin-17/immunology , Interleukin-23/genetics , Interleukin-23/immunology , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Mice , Mice, Inbred C57BL , Psoriasis/chemically induced , Psoriasis/genetics , Psoriasis/pathology , Receptors, Antigen, T-Cell, gamma-delta/genetics , Receptors, Antigen, T-Cell, gamma-delta/immunology , Skin/immunology , Skin/innervation , T-Lymphocytes/immunology , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/immunologyABSTRACT
A body type with a high waist circumference or elevated waist-to-hip ratio (WHR), known as the "apple" body type, represents central/visceral obesity and is associated with the metabolic syndrome. The aim of this study was to simultaneously investigate the body mass index (BMI) and WHR in order to classify body types in individuals with hidradenitis suppurativa (HS) compared with a general dermatological population. A hospital-based cross-sectional study was performed in the Netherlands. One hundred and six HS patients and 212 controls were included. The BMI was significantly higher in the HS group in comparison with the control group, at 27.8 ± 5.4 and 25.6 ± 4.8, respectively (P < 0.001). The WHR did not significantly differ between HS patients and the control dermatological population (P > 0.05). A more peripheral pattern of bodyweight distribution was seen in 43% of the 37 obese HS individuals, in contrast to 19% of 31 obese patients in the control group (P = 0.036). In conclusion, the body type in obese HS patients, based on the WHR, shows a more peripheral pattern and differs from the WHR in the BMI-matched general dermatological population.
Subject(s)
Hidradenitis Suppurativa/complications , Metabolic Syndrome/complications , Obesity/complications , Waist-Hip Ratio , Adolescent , Adult , Aged , Case-Control Studies , Child , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
Clinical improvement of psoriasis induced by IL-4 treatment has been ascribed to changes in dermal inflammatory cells, such as activation of Th2 cells and tolerization of dendritic cells by suppressing IL-23 production. The pathologic epidermal alterations in psoriatic lesional skin include increased epidermal expression of IL-1ß, IL-6, S100A7, and human ß-defensin 2 (hBD2) and a downregulated expression of the epidermal transcription factor GATA3. Effects of IL-4 on the epidermal compartment of psoriasis lesions were not previously investigated. Therefore, we investigated whether IL-4 directly affects abovementioned psoriatic markers in the epidermal compartment. We cultured freshly isolated psoriatic epidermal cells, whole psoriatic and healthy skin biopsies, human keratinocytes and Langerhans cells with IL-4. The secretion of IL-1ß and IL-6 by psoriatic epidermal cells was inhibited by IL-4 via transcriptional and posttranscriptional mechanisms, respectively. In normal skin, IL-4 inhibited IL-1ß- and IL-17A-induced hBD2 expression in vitro. In addition, IL-4 reduced the protein expression of hBD2 in psoriatic skin biopsies and induced phospho-STAT6 protein. Epidermal GATA3 mRNA and protein were significantly upregulated by IL-4 in epidermal cells and keratinocytes. Our data argue that IL-4 improves psoriasis not only via modification/induction of Th2 cells and type II dendritic cells, but also via direct inhibition of inflammatory cytokines in resident IL-4R-expressing epidermal cells and thereby alters the psoriatic skin phenotype toward a healthy skin phenotype.
