Schoepe S.,Common Mechanism Research Berlin |
Schoepe S.,Bayer AG |
Schacke H.,Common Mechanism Research Berlin |
Bernd A.,Goethe University Frankfurt |
And 3 more authors.
Skin Pharmacology and Physiology
Topical glucocorticoids (GCs) demonstrate good anti-inflammatory effects but are limited by their side effect potential, with skin atrophy being the most prominent one. Thus, determining the atrophogenic potential of novel compounds is important. The aim of this study was to establish an in vitro skin atrophy model. A screening cascade was applied and GCs with a known atrophogenic potential were used as tool compounds. Five rodent and human cutaneous cell types/cell lines and 2 human skin equivalents were tested. Known and suspected atrophy markers related to collagen metabolism and epidermal thickness were measured. Altogether, a combination of 7 different cellular assays with up to 16 markers each were investigated. A reproducible, more than 2-fold, regulation of the candidate markers by dexamethasone or clobetasol was found for: (a) matrix metalloproteinase (MMP) 1, 2, 3 and 9 expression in human keratinocytes, (b) COL1A1 and COL3A1 expression in 3T3 fibroblasts, and (c) epidermal thickness, collagen and MMP synthesis in the full-thickness skin model (FTSM). These 3 models were further investigated with a panel of 4-5 GCs, demonstrating dose dependency and correlation with the atrophogenic potential of the tool compounds, qualifying them as potentially suitable. Finally, the predictability of these models for the in vivo situation was analyzed, testing a novel selective GC receptor agonist (SEGRA) in comparison to clobetasol. The results from the in vitro models suggested less atrophogenic effects for the SEGRA compound, which indeed was confirmed in the hr/hr rat skin atrophy model. In conclusion, a combination of 3 in vitro models based on 3T3 cells, human keratinocytes and FTSM with several readouts is recommended to determine atrophogenicity of GC receptor ligands. Further experiments are necessary to eventually reduce this panel and to demonstrate the true predictability for the clinic. ©2009 S. Karger AG, Basel. Source
Gross D.,Charite - Medical University of Berlin |
Schmitz A.A.,Bayer AG |
Vonk R.,Bayer AG |
Igney F.H.,Novartis |
And 6 more authors.
Biopreservation and Biobanking
There is a rising need for biomaterial in dermatological research with regard to both quality and quantity. Research biobanks as organized collections of biological material with associated personal and clinical data are of increasing importance. Besides technological/methodological and legal aspects, the willingness to donate samples by patients and healthy volunteers is a key success factor. To analyze the theoretical willingness to donate blood and skin samples, we developed and distributed a questionnaire. Six hundred nineteen questionnaires were returned and analyzed. The willingness to donate samples of blood (82.5%) and skin (58.7%) is high among the population analyzed and seems to be largely independent of any expense allowance. People working in the healthcare system, dermatological patients, and higher qualified individuals seem to be in particular willing to donate material. An adequate patient insurance as well as an extensive education about risks and benefits is requested. In summary, there is a high willingness to donate biological samples for dermatological research. This theoretical awareness fits well with our own experiences in establishing such a biobank. © 2011, Mary Ann Liebert, Inc. Source
Weitz M.,Humboldt University of Berlin |
Kiessling C.,Humboldt University of Berlin |
Friedrich M.,Humboldt University of Berlin |
Prosch S.,Humboldt University of Berlin |
And 8 more authors.
Background: Previously, we have reported a frequent association of active plaque psoriasis with inflammation-mediated cytomegalovirus (CMV) reactivation. Objectives: This study aimed at characterizing the impact of CMV infection on psoriasis disease activity and peripheral cellular adaptive immune response. Patients/Methods: Twenty nine patients with active plaque psoriasis and 29 healthy controls were analysed for CMV-serostatus, CMV-antigenaemia, frequencies of peripheral CMV-specific T cells and the immunophenotype of peripheral CD8+ T cells. Results: (i) Psoriasis severity was higher in CMV-seropositive patients and positively correlated to the severity of CMV-antigenaemia. (ii) In comparison to CMV-seropositive healthy controls, CMV-seropositive psoriasis patients showed a reduced frequency of circulating CMV-specific T cells that increased under effective antipsoriatic therapy. (iii) The immunophenotype of peripheral CD8+ T cells was dominated by CMV-seroprevalence. (iv) Selective analysis of CMV-seronegative psoriasis patients revealed a strong expansion of a - probably early activated - CD8+ T-cell population with the yet undescribed differentiation phenotype 'CD45RA-dim/CD11a-dim'. Under effective antipsoriatic therapy this population decreased in parallel to an increase of effector differentiated CD8+ T cells. Conclusions: Taken together with our previous results of inflammation-mediated CMV reactivation in psoriasis, our data support the concept of an interactive relationship between psoriasis and CMV infection which may be mediated by peripheral CD8+ T cells. © 2011 John Wiley & Sons A/S. Source