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Lesional Psoriatic Skin (lesional + psoriatic_skin)
Selected AbstractsVascular adhesion protein-1 (VAP-1) is overexpressed in psoriatic patientsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2007A Madej Abstract Background, Vascular adhesion protein (VAP)-1 is an adhesion molecule with an enzymatic activity that partakes in the migration process of lymphocytes. Objectives, The aim of this study was to investigate the expression of VAP-1 in the skin and serum of psoriatic patients. Material and methods, Seventy-one patients suffering from psoriasis aged between 23 and 89 years were included in the study. The mean psoriasis severity assessed according to the psoriasis area and severity index was 14.2 ± 9.6 points. The soluble VAP-1 serum concentration was evaluated by ELISA and VAP-1 expression in the skin (nine patients) immunohistochemically. Results, The serum concentration of soluble VAP-1 was significantly higher in psoriatic patients than in healthy controls (403.4 ± 130.8 ng/mL vs. 246.4 ± 68.0 ng/mL; P < 0.0001). No significant relationships were found between sVAP-1 concentration and studied clinical parameters, except the presence of pruritus. Mean number of VAP-1 positive vessels in psoriatic skin, both lesional (19.8 ± 1.4) and non-lesional (9.4 ± 1.4), was significantly higher than in healthy skin (5.4 ± 1.5; P < 0.005). Lesional psoriatic skin demonstrated significantly more VAP-1 positive vessels than non-lesional skin (P < 0.01). Conclusions, Significant overexpression of VAP-1 in both lesional and non-lesional psoriatic skin and higher serum level of soluble VAP-1 in psoriatic patients may indicate the role of VAP-1 in chronic inflammation occurring in psoriasis. However, because of lack of correlation between soluble VAP-1 serum levels and psoriasis severity this hypothesis needs further investigation. [source] Adalimumab therapy rapidly inhibits p38 mitogen-activated protein kinase activity in lesional psoriatic skin preceding clinical improvementBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2010L. Soegaard-Madsen Summary Background, The pathogenesis of psoriasis and the mechanisms of action of antitumour necrosis factor (TNF)-, therapies are incompletely understood. Objectives, To investigate the early molecular effects of adalimumab in psoriatic skin. Methods, Biopsies taken from patients with psoriasis were examined before and after the onset of adalimumab therapy. TNF-, protein level and mRNA expression were measured by enzyme-linked immunosorbent assay and quantitative reverse transcription,polymerase chain reaction, respectively. The activities of p38 mitogen-activated protein kinase (MAPK) and extracellular regulated kinase 1 and 2 (ERK1/2) as well as the downstream kinases MAPK-activated protein kinase 2 (MK2) and mitogen- and stress-activated protein kinase 1 and 2 (MSK1/2) were measured by Western blot analyses. Results, We demonstrated that clinical and histological improvements were detected from day 14. The increased activity of p38 MAPK in lesional psoriatic skin was significantly inhibited by adalimumab already at day 4. The activities of ERK1/2, MSK1/2 and MK2 were reduced at the end of study (day 84) when the level of TNF-, in lesional psoriatic skin reached the nonlesional level, and the Psoriasis Area and Severity Index score was reduced. Conclusions, The rapid inhibition of p38 MAPK by adalimumab in lesional psoriatic skin preceded clinical and histological improvements, demonstrating an association between TNF-, neutralization and p38 MAPK inhibition. Thus, inhibition of p38 MAPK may be a novel mechanism by which adalimumab mediates its antipsoriatic effect. [source] Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease activity and abnormal differentiation of keratinocytes in psoriasisBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2006S. Benoit Summary Background, The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. Objectives, We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. Methods, Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. Results, A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of <15 showed serum levels of 705 ± 120 ng mL,1 (mean ± SEM, n = 18), those with a PASI of ,15 showed levels of 1315 ± 150 ng mL,1 (n = 32) while controls presented with 365 ± 50 ng mL,1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional, nonpsoriatic interfollicular epidermis. Conclusions, Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions. [source] The mitogen-activated protein kinases p38 and ERK1/2 are increased in lesional psoriatic skinBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2005C. Johansen Summary Background, Alterations in specific signal transduction pathways may explain the hyperproliferation and abnormal differentiation of the keratinocytes as well as the increased expression of inflammatory cytokines seen in psoriasis. Major signalling pathways used by eukaryotic cells to transduce extracellular signals into cellular responses impinge on the mitogen-activated protein kinases (MAPKs). Objectives, To investigate the expression of the MAPK p38, extracellular signal-regulated kinase (ERK) and c-Jun NH2 -terminal kinase (JNK) in psoriatic skin. Methods, Keratome biopsies were taken from patients with plaque-type psoriasis. Western blot analysis was used to determine p38, ERK and JNK activity and protein levels, whereas kinase assays were used to examine the kinase activity of p38. Results, We demonstrated increased levels of the phosphorylated forms of p38 and ERK1/2 in lesional psoriatic skin compared with nonlesional psoriatic skin. No abnormality was found in the activation and expression of JNK1/2. Ex vivo kinase assays confirmed the increased activation of p38, and furthermore demonstrated increased kinase activity of the p38 isoforms p38,, p38, and p38, in lesional compared with nonlesional psoriatic skin. p38, was not detected in the psoriatic skin. Clearance of the psoriatic lesions, induced by climatotherapy at the Dead Sea for 4 weeks, led to a normalization in the activity of both p38 and ERK1/2. Conclusions, Taken together, our results demonstrate that the activity of the MAPKs p38,, p38, and p38, and ERK1/2 are increased in lesional psoriatic skin compared with nonlesional psoriatic skin, and that clearance of psoriasis normalizes the p38 and ERK1/2 activity. Thus, p38 and ERK1/2 might be potential targets in the treatment of psoriasis. [source] | ||||||||||