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Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum.

ABSTRACT: S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measured by psoriasis area and severity index (PASI) and serum protein levels of S100A8/A9 were repeatedly analyzed. Narrowband-UVB treatment significantly reduced S100A8, S100A9 gene expression and S100A8/A9 protein levels in lesional skin while serum levels showed no significant change. No correlation between PASI and serum S100A8/A9 protein levels was found. These results implicate a role of S100A8/A9 in the anti-inflammatory effect of narrowband-UVB. Serum S100A8/A9 levels do not respond to treatment suggesting that serum S100A8/A9 does not originate from psoriasis skin keratinocytes. Serum S100A8/A9 levels do not correlate with PASI questioning serum S100A8/A9 as a biomarker for psoriasis skin activity. Trial Registration: DRKS 00014817.

SUBMITTER: Duvetorp A

PROVIDER: S-EPMC6415841 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum.

Duvetorp Albert A Söderman Jan J Assarsson Malin M Skarstedt Marita M Svensson Åke Å Seifert Oliver O

PloS one 20190313 3

S100A8 and S100A9 proteins are highly upregulated in patients with psoriasis and have been proposed as potential biomarkers for psoriasis. The present study was designed to analyze the effect of narrowband ultraviolet B therapy on these proteins. S100A8, S100A9 gene expression and S100A8/A9 heterocomplex protein levels were analyzed in lesional and non-lesional skin before and after narrowband-UVB treatment in patients with chronic plaque type psoriasis. In addition, disease severity was measure ...[more]

PMID: 30865695

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Project description:BackgroundMyocardial infarction (MI) triggers myelopoiesis, resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear.MethodsUsing a mouse model of the permanent ligation of the left anterior descending artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of the acute inflammatory response and the underlying signaling pathways. Using a combination of genetic and pharmacological strategies, we identified the sequelae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indexes of neutrophilia with major adverse cardiovascular events was studied in a cohort of patients with acute MI.ResultsInduction of MI results in rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll-like receptor 4 and prime the nod-like receptor family pyrin domain-containing 3 inflammasome in naïve neutrophils and promote interleukin-1β secretion. The released interleukin-1β interacts with its receptor (interleukin 1 receptor type 1) on hematopoietic stem and progenitor cells in the bone marrow and stimulates granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and their downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome, higher neutrophil count on admission and after revascularization correlates positively with major adverse cardiovascular disease outcomes.ConclusionsOur study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response after myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or their downstream mediators (eg, nod-like receptor family pyrin domain-containing 3 inflammasome, interleukin-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in patients with acute coronary syndrome.

Dataset Information

Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum.

Publications

Observational study on Swedish plaque psoriasis patients receiving narrowband-UVB treatment show decreased S100A8/A9 protein and gene expression levels in lesional psoriasis skin but no effect on S100A8/A9 protein levels in serum.

Similar Datasets

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