Protein biomarker quantification in psoriatic SC detects key pathophysiological mechanisms and enables noninvasive drug profiling in translational medicine settings.
Stratum corneum collected by tape stripping from 10 and 24 subjects with cutaneous T‐cell lymphomas (CTCL) or psoriasis, respectively, were compared using quantitative label‐free mass spectrometry analysis. A non‐supervised statistical analysis (Posneg NMF) based on 352 differentially expressed proteins in both CTCL and psoriasis samples was able to separate the two disease groups and finally able to identify a set of 112 proteins that contributed most and significantly to the separation when compared to non‐lesional samples. In addition, Luminex assay revealed that the increase in the amount of chemokines related to the inflammatory response, and immune cell infiltration and recruitment in lesional stratum corneum in CTCL, including CXCL8, CXCL9, CXCL10, CCL27, TNF and sICAM‐1 was in agreement with published data on entire skin biopsies. Proteome analysis using quantitative methods including mass spectrometry and Luminex technology offered the possibility to investigate the relevant protein signature in CTCL and may be helpful to diagnose and investigate the efficacy of treatments in clinical investigations using non‐invasive methods in future.
We investigated UV-induced signalling in an ex vivo skin organ culture model using phospho-antibody array. Phosphorylation modulations were analysed in time-course experiments following exposure to solar-simulated UV and validated by Western blot analyses. We found that UV induced P-p38 and its substrates, P-ERK1/2 and P-AKT, which were previously shown to be upregulated by UV in cultured keratinocytes and in vivo human skin. This indicates that phospho-antibody array applied to ex vivo skin organ culture is a relevant experimental system to investigate signalling events following perturbations. As the identified proteins are components of pathways implicated in skin tumorigenesis, UV-exposed skin organ culture model could be used to investigate the effect on these pathways of NMSC cancer drug candidates. In addition, we found that phospho-HCK is induced upon UV exposure, producing a new candidate for future studies investigating its role in the skin response to UV and UV-induced carcinogenesis.
increased. CXCL10 (IP-10) and CXCL9 (Mig), known to attract Th1 cells and promote their maturation through interaction with CXCR3 7 were both significantly increased. Likewise, the CCL20 (MIP-3alpha), known to be increased in injured keratinocytes in response to Th2 and Th17 activation, was found to be elevated. This observation is in line with previous data on early papule biopsies. 8 In addition, CCL chemokines involved in the recruitment of T cells, monocytes and dendritic cells such as CCL3, CCL4, CCL5, CCL7 and CCL27 were also found modulated.In contrast, a decrease in the amount of interleukin 1 alpha (IL1A) in lesional SC was observed. Interestingly, these findings have also been reported in SC of other inflammatory diseases, such as psoriasis, but not in acne. 2 Epidermal growth factor (EGF) and CX3CL1 (fractalkine) were found slightly but significantly decreased in lesional SC. EGF was recently proposed for the treatment of scarring acne lesions to attenuate the expression of inflammatory cytokines in human epidermal keratinocytes exposed to Propionibacterium acnes. 9,10 IL1ra, significantly increased in lesional SC, is known to be secreted by various types of cells including immune cells, epithelial cells and adipocytes; it is a natural inhibitor of the pro-inflammatory effect of IL1A and interleukin 1beta (IL1B) and modulates a variety of interleukin 1 related immune and inflammatory responses.Importantly, we have demonstrated that the most relevant biological processes were related to neutrophils, T cells, monocytes and dendritic cells recruitment in the stratum corneum, as it has been demonstrated in lower skin layers through biopsies. Additionally, our results suggest that the strongly induced CXCL8, MPO and MIF may be used as SC biomarkers of acne through non-invasive technique.In conclusion, the highlighted profile of changes in proteins, chemokines and cytokines is in line with previously published data for punch biopsies of acne lesions. This supports the use of non-invasive strip biopsies as a reliable tool for quantification of key factors of inflammation for clinical investigations in acne vulgaris. As the sample size was low, his experimental study should be confirmed by a larger study in the future.The studies have been financed by Galderma R&D, Sophia Antipolis, France. P.B., J.J.V., A.M. and B.M. designed this study. C.Q.-R. performed (tape stripping) samples collection. B.M. performed protein extraction from tape stripping. A.S. performed the Luminex assays and quality controls. B.G. performed data and statistical analyses. A.M., S.B.-R. and B.M. wrote the manuscript.
Background: The etiology and different inflammatory steps associated with the development of an acne nodule remain unsolved. Objectives: This study aimed to investigate the main biological processes involved in acne nodules and compare them to those of papules. Methods: Nodules, papules, and non-involved skin of the back (control) were biopsied to perform proteomic analysis using mass spectrometry, Luminex assay, and elastase staining on skin sections. Results: Many factors involved in the migration and function of immune cells, particularly those impacting leukocytes and neutrophils, were strongly and significantly higher in nodules than in papules and non-involved skin, while several enzymes involved in lipid metabolism were lower. Elastase staining confirmed strong neutrophil infiltration within and around the nodules. Conclusions: Our results highlight the role of neutrophils during nodule formation in severe nodular acne of the back.
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