Expression of pigment epithelium-derived factor in psoriasis, verrucae, squamous cell carcinoma and normal skin: An immunohistochemical study.

BACKGROUND: Preservation of homeostasis status in the skin needs an equilibrium of keratinocyte proliferation, differentiation, necrosis and apoptosis. Disturbance of these regulatory mechanisms may lead to keratinocyte neoplastic and hyperproliferative diseases. Pigment epithelium-derived factor is a glycoprotein that is endogenously produced in different tissues and has a variety of biological effects in different diseases. OBJECTIVE: To evaluate the keratinocyte expression of pigment epithelium-derived factor in normal skin and three epidermal hyperproliferative diseases, namely, psoriasis, verrucae and squamous cell carcinoma. METHODS: This study included skin biopsy samples from 80 participants who were divided into four equal groups; each containing 20 samples. The first group included skin biopsies from normal skin, the second group from psoriatic lesions, the third group from verruca vulgaris and the fourth group from squamous cell carcinoma. All tissue samples were stained with hematoxylin and eosin stain and later immunohistochemically for pigment epithelium-derived factor expression. RESULTS: Scores of pigment epithelium-derived factor expression were lower in squamous cell carcinoma and verruca and psoriasis than normal skin with a significant difference (P = 0.04). In addition, the pattern of pigment epithelium-derived factor expression was mainly cytoplasmic in normal skin with a significant difference with that seen in psoriasis, squamous cell carcinoma and verruca vulgaris (P = 0.001). CONCLUSION: Pigment epithelium-derived factor may play a role in keratinocyte differentiation.

Evaluation of Toll-like receptor expression profile in patients with psoriasis vulgaris.

TLRs are thought to play a role in the pathophysiology of such dermatological diseases as leprosy, acne and psoriasis. The study included 20 patients with plaque psoriasis, as well as 20 healthy age- and gender-matched control subjects. Real-time polymerase chain reaction evaluation was made of the messenger RNA expression of TLRs 1-10 in lesional tissue and peripheral blood mononuclear cell samples in psoriasis patients. TLR 3, 5, 6, 7, 9 and 10 lesional tissue mRNA expressions were increased significantly when compared to the expression levels in the PBMCs of the same patients (p = 0.0082, p = 0.0176, p = 0.0239, p = 0.0261, p = 0.0223, p = 0.0206). A comparison of the TLR expression in the PBMCs of healthy subjects and the PBMCs of patients with psoriasis showed a significant increase in the TLR 1, 8 and 10 mRNA expressions in the patient group (p < 0.0001, p < 0.0001, p = 0.0035). The TLR 5 mRNA expression was significantly higher in the control group than in the patient group (p = 0.0037). To the best of our knowledge, this is the first study in literature to evaluate mRNA TLR expression levels in the lesional tissue and PBMCs of patients with psoriasis.

Is there a correlation of serum and tissue T helper-1 and -2 cytokine profiles with psoriasis activity and severity? A cross-sectional study.

BACKGROUND: Previous studies correlating Th1 and Th2 cytokine profiles with psoriasis activity provided inconsistent results. Correlation of tissue cytokine levels with psoriasis severity has not been studied till now. OBJECTIVE: To compare serum and tissue Th1 and Th2 cytokine profiles of patients with active and stable psoriasis as well as healthy controls, and to correlate them with psoriasis severity. METHODOLOGY: This was a cross-sectional study involving adult patients with 'active' psoriasis (untreated progressive chronic plaque psoriasis, guttate psoriasis, and erythrodermic psoriasis), 'stable' psoriasis (stable plaque psoriasis or those with completely resolved lesions) and healthy subjects with non-inflammatory skin lesions as controls. Mean levels of Th1 and Th2 cytokines in serum [interleukin 2 (IL-2), interferon-gamma (IFN-γ), IL-4, IL-10] and tissue mRNA expression (IFN-γ, IL-4) were compared among these three groups. RESULTS: There were 30 patients each in active and stable psoriasis groups, and 15 in the control group. Mean serum IL-2, IFN-γ, and IL-10 levels of patients with psoriasis patients were significantly higher than the controls (P < 0.001 for both active and stable psoriasis), whereas mean serum IL-4 level of patients was significantly lower than the controls (P < 0.001). However, there was no statistically significant difference of serum cytokine levels between active and stable psoriasis groups. Mean quantitative tissue mRNA expression of IFN-γ and IL-4 of patients with active and stable psoriasis were significantly lower than the controls (P < 0.001 and <0.01, respectively), but were not significantly different between active and stable psoriasis groups. Serum and tissue cytokines showed weak correlation with psoriasis area and severity index. LIMITATIONS: Small sample size and heterogenous nature of patients with psoriasis in terms of disease activity, morphology and treatment are limitations of this study. CONCLUSIONS: There is no significant change in the serum or tissue levels of Th1 and Th2 cytokines with activity or severity of psoriasis.

Receptor for advanced glycation end products is overexpressed in psoriatic plaques independent of disease severity.

BACKGROUND: Enhanced expression and excitation of the receptor for advanced glycation end products is considered to play a role in the regulation of many pro-inflammatory genes involved in the pathogenesis of psoriasis. AIM: We investigated the expression of receptor for advanced glycation end product in various cell types, in lesional and peri-lesional skin of patients with psoriasis, and its correlation with disease severity. METHODS: Paraffin-embedded punch biopsy tissue taken from psoriatic plaques and peri-lesional normal appearing skin tissue of twenty patients with psoriasis, and normal skin samples of eleven healthy participants, were enrolled in the study. The sections were stained immunohistochemically with anti-receptor for advanced glycation end product antibody. The intensity of receptor for advanced glycation end product expression was assessed semi-quantitatively on epidermal cells, microvascular endothelium, dermal fibroblasts and inflammatory cells. They were graded as follows: 0 (no staining), 1 (weak), 2 (moderate) and 3 (strong) intensity. RESULTS: Receptor for advanced glycation end product expression on epidermis, microvascular endothelium, inflammatory cells and fibroblasts in the psoriatic plaques was more intense than perilesional and normal tissue (all P < 0.05). It did not correlate with disease severity. LIMITATIONS: The main limitation of our study is that this was a semi-quantitative assessment, detected immunohistochemically in skin biopsies. CONCLUSION: Receptor for advanced glycation end product expression may have an important role in psoriasis pathogenesis, independent of disease severity.

Anti-proliferative and anti-inflammatory effects of 3ß,6ß,16ß-Trihydroxylup-20(29)-ene on cutaneous inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: 3ß,6ß,16ß-Trihydroxylup-20(29)-ene (TTHL) is a triterpene isolated from the flowers of Combretum leprosum, a plant used in folk medicine in the north of Brazil for the treatment of skin disorders. AIM OF THE STUDY: In the present study, TTHL was evaluated as a potential topical anti-inflammatory and anti-proliferative agent through in vivo and in vitro models. MATERIAL AND METHODS: Anti-inflammmatory and anti-proliferative effects of TTHL were assessed using Swiss mice in acute and chronic models of skin inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA) application. Anti-proliferative activity was proved through in vitro experiments with the HaCaT human keratinocyte cell line. RESULTS: Treatment with TTHL inhibited inflammatory parameters such as oedema formation and cellular infiltration in acute and chronic models. In the chronic model, TTHL also inhibited epidermal hyperproliferation, as evidenced by reduction of epidermis thickness and proliferating cell nuclear antigen expression. The anti-proliferative effect was confirmed by the capability of TTHL in reducing the proliferation and inducing cell apoptosis of HaCaT cells. Suggesting a mechanism of action, TTHL showed activation of corticosteroid receptors, but without the induction of corticosteroid-related cutaneous side effects. CONCLUSION: Our results demonstrate consistent anti-inflammatory and anti-proliferative activity and assign TTHL as a valuable tool in the development of a new treatment for skin inflammatory and proliferative diseases, such as psoriasis.

Local antimicrobial, protease and cytokine defense systems in psoriatic skin.

BACKGROUND: Psoriasis vulgaris is an inflammatory skin condition characterized by dramatic biochemical and immunological changes. AIMS: The aim of the study was to evaluate antimicrobial response, tissue degeneration reactions and distribution of inflammatory cytokines in untreated psoriatic skin as well as the correlations between these factors and influence on the course of the disease. METHODS: We evaluated skin samples obtained from routine punch biopsies in 40 patients with psoriasis vulgaris. All tissue specimens were examined by hematoxylin and eosin staining and immunohistochemistry for human beta defensin 2 (HBD-2), matrix metalloproteinase 2 (MMP-2), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8. The staining intensity was semi-quantitatively graded. RESULTS: Numerous keratinocytes, fibroblasts and macrophages expressed HBD-2 while the number of MMP-2-positive macrophages, fibroblasts and epitheliocytes varied. TNF-alpha-positive cells varied from a few to numerous in each microscopic field. IL-6-positive cells varied from a few to abundant and IL-8-positive cells from numerous to abundant in each field. LIMITATIONS: This study had a rather small patient number. CONCLUSIONS: Psoriatic skin shows a strong correlative increase in skin antimicrobial proteins and enzymes mediating tissue degeneration suggesting that the skin maintains compensatory mechanisms during persistent remodeling. While individual notable decrease in antimicrobial proteins was observed in some tissue samples, generally the increased human beta defensin associated with psoriasis is likely to be due to an altered immune status. TNF-alpha, IL-6 and IL-8 are common cytokines expressed in psoriatic skin plaques to maintain the inflammatory cycle. HBD-2, MMP-2 and TNF-alpha positively correlate with the severity of psoriasis. Meanwhile, the expression of IL-8 significantly decreases with clinically more severe psoriasis, perhaps making these factors candidate prognostic factors for psoriatic inflammation.

Medicina darwiniana y psoriasis / Darwinian Medicine and Psoriasis

La medicina evolutiva o darwiniana entiende algunos procesos patológicos como intentos del organismo por solucionar un problema o generar mecanismos de defensa. Algunas enfermedades pueden haber representado una ventaja en ciertos estadios de la evolución humana. La psoriasis es una enfermedad poligénica con alta penetrancia y una prevalencia de hasta el 3% en las poblaciones de origen caucásico. Se ha descrito que las lesiones de psoriasis generan una mayor capacidad para la curación de las heridas, y de lucha contra la infección. Se ha postulado que, en ciertas poblaciones, los genes promotores de psoriasis han sido seleccionados ante la presión ambiental de ciertas infecciones como la lepra, el sida y la tuberculosis. La tendencia de los enfermos con psoriasis grave al desarrollo de síndrome metabólico puede representar un intento de reacción ante presiones ambientales y señales de alarma que desencadenan resistencia insulínica y ahorro de grasa

Darwinian medicine, or evolutionary medicine, regards some pathological conditions as attempts by the organism to solve a problem or develop defense mechanisms. At certain stages of human evolution, some diseases may have conferred a selective advantage. Psoriasis is a high-penetrance multigenic disorder with prevalence among whites of up to 3%. Psoriatic lesions have been linked with enhanced wound-healing qualities and greater capacity to fight infection. Leprosy, tuberculosis, and infections caused by viruses similar to human immunodeficiency virus have been postulated as environmental stressors that may have selected for psoriasis-promoting genes in some human populations. The tendency of patients with severe psoriasis to develop metabolic syndrome may reflect the body’s attempt to react to environmental stresses and warning signs by triggering insulin resistance and fat storage

Prevalence of metabolic syndrome in patients with psoriasis.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and is associated with an increased risk of cardiovascular atherosclerosis. Metabolic syndrome, a conglomerate of various clinical and biochemical parameters is a significant predictor of atherosclerotic disease and the associated risk for cardiovascular events in such patients. AIM: To investigate the prevalence of metabolic syndrome in patients with psoriasis. METHODS: The study was a prospective, hospital based case-control study involving 150 adult patients with chronic plaque psoriasis and 150 healthy controls. Venous samples were taken at the enrollment visit after the subjects had fasted overnight (at least 8 h). Serum cholesterol and triglycerides were measured with enzymatic procedures. Plasma glucose was measured using a glucose oxidase method. Metabolic syndrome was diagnosed by the presence of three or more criteria of the National Cholesterol Education Programme's Adult Panel III (ATP III). Statistical analysis of the data was done using statistical processing software (SPSS-17) and epi-info software. RESULTS: Metabolic syndrome was significantly more common in psoriatic patients than in controls 42(28%) vs 9(6%), odds ratio (OR) = 6.09, P<0.05. Psoriatic patients also had a significantly higher prevalence of hypertriglyceridaemia (73/150 among cases vs 24/150 among controls; P<0.05), arterial hypertension (74/150 among cases vs 24/150 among controls; P<0.05) and impaired fasting plasma glucose levels (27/150 among cases vs 04/150 among controls; P<0.05). Psoriatic patients with metabolic syndrome had mean disease duration of 13.67±11.87 years against 6.46±5.80 years in those without metabolic syndrome. CONCLUSION: There is a significantly higher prevalence of metabolic syndrome in psoriasis patients as compared to general population and so is the risk of having atherosclerotic adversity. While managing the psoriatic plaques of these patients, concerns should extend to the atherosclerotic plaques as well.

Is CCR7 a potential target for biologic therapy in psoriasis? Increased expression of CCR7 in psoriasis vulgaris.

BACKGROUND: Activated T cells present in psoriatic plaques play a key role in the pathogenesis of psoriasis. CCR7 on T cells plays a crucial role in native immune response and formation of secondary lymphoid organ. AIMS: To determine whether differential expression and functions of the CCR7 occur in psoriasis patients in China, we examined CCR7 on T cells from normal and psoriasis subjects. METHODS: Skin specimens and T cells from 33 patients and 22 healthy controls were analyzed by immunohistology, flow cytometry, and RT-PCR. RESULTS: Patients with psoriasis had a skewed distribution of T lymphocytes, with an increased level of CCR7+ T lymphocytes compared to healthy controls (P<0.01) By flow cytometry, it was found that CCR7 was selectively, frequently, and functionally expressed on CD4+ (20.5+/-6.8%)but not on CD8+ (9.5+/-3.4%) T cells from patients with psoriasis, whereas this phenomenon was not seen in normal subjects. Through RT-PCR it was also found that CCR7 was highly expressed on T cells in patients with psoriasis than in healthy controls in the level of gene. CONCLUSIONS: Patients with psoriasis had a skewed distribution of T lymphocytes, with an increased level of CCR7+ T lymphocytes compared to healthy controls. CD4+ CCR7+ T cells had abnormal expression, which might induce protraction and persistence of psoriasis.