IL-17C amplifies epithelial inflammation in human psoriasis and atopic eczema.

BACKGROUND: Key pathogenic events of psoriasis and atopic eczema (AE) are misguided immune reactions of the skin. IL-17C is an epithelial-derived cytokine, whose impact on skin inflammation is unclear. OBJECTIVE: We sought to characterize the role of IL-17C in human ISD. METHODS: IL-17C gene and protein expression was assessed by immunohistochemistry and transcriptome analysis. Primary human keratinocytes were stimulated and expression of cytokines chemokines was determined by qRT-PCR and luminex assay. Neutrophil migration towards supernatant of stimulated keratinocytes was assessed. IL-17C was depleted using a new IL-17C-specific antibody (MOR106) in murine models of psoriasis (IL-23 injection model) and AE (MC903 model) as well as in human skin biopsies of psoriasis and AE. Effects on cell influx (mouse models) and gene expression (human explant cultures) were determined. RESULTS: Expression of IL-17C mRNA and protein was elevated in various ISD. We demonstrate that IL-17C potentiates the expression of innate cytokines, antimicrobial peptides (IL-36G, S100A7 and HBD2) and chemokines (CXCL8, CXCL10, CCL5 and VEGF) and the autocrine induction of IL-17C in keratinocytes. Cell-free supernatant of keratinocytes stimulated with IL-17C was strongly chemotactic for neutrophils, thus demonstrating a critical role for IL-17C in immune cell recruitment. IL-17C depletion significantly reduced cell numbers of T cells, neutrophils and eosinophils in murine models of psoriasis and AE and led to a significant downregulation of inflammatory mediators in human skin biopsies of psoriasis and AE ex vivo. CONCLUSION: IL-17C amplifies epithelial inflammation in Th2 and Th17 dominated skin inflammation and represents a promising target for the treatment of ISD.

Metallothionein isoform gene expression in zinc-treated human peripheral blood lymphocytes.

Zinc plays an important role in the maintenance of the immune system. While the mechanisms of zinc ions interaction with immune cells are still poorly understood, a striking concurrent effect of zinc is the induction of the biosynthesis of metallothioneins (MT), a group of low molecular weight, cysteine-rich metal-binding proteins, believed to play a role in zinc homeostasis. In humans, they are encoded by a family of genes, located at 16q13 containing 10 functional and 7 non-functional MT isoforms. In this work we analyzed the spectrum of different isoforms in human peripheral blood lymphocytes. It was demonstrated by RT-PCR that the MT-2a, MT-1a, MT-1e, MT-1f, MT-1g, MT-1h and MT-1x genes are expressed in these cells and that these isoforms are further upregulated by zinc, as examined by quantitative RT-PCR. Surprisingly, RT-PCR also showed the presence, even in unstimulated cells, of MT-3 transcripts, which are considered as brain-specific isoforms. In an effort to determine whether MTmRNA abundance is translated into MT protein, MT isolated from zinc-treated lymphocytes by gel chromatography was resolved into 7 metal-binding fractions by using RP-HPLC. Automatic Edman-degradation of the different fractions revealed the presence of MT-2a, MT-1a, MT-1e, MT-1f, MT-1g, MT-1h, MT-1x and MT-1k, an isoform which until now was only identified at the level of protein in human liver and kidney tissue.

Bcl-2 expression in human melanocytes and melanocytic tumors.

During an immunohistochemical study of the distribution of the Bcl-2 proto-oncogene product in frozen sections of normal human skin, a hitherto unrecognized strong reactivity with melanocytes was observed. This prompted us to study Bcl-2 expression in a variety of pigment lesions. In nevocellular nevi, immunoreactivity gradually diminished or even disappeared toward the deeper dermal component. In malignant melanomas of all stages and histological subtypes, the neoplastic cells expressed Bcl-2 oncoprotein, the most intense positivity being restricted to cells in the radial growth phase. Cutaneous and lymph node metastases of malignant melanomas were negative or showed only weak and focal reactivity. The specificity of the staining was confirmed by Western blotting of tissue lysates. The loss of Bcl-2 expression in the deeper parts of nevi may offer an explanation for the "maturation" and final disappearance of dermal nevocellular nevi. The expression of Bcl-2 oncoprotein by malignant melanomas adds these neoplasms to a growing list of tumors expressing this oncoprotein. Bcl-2 in malignant melanoma may play a role in tumor development by sparing the cells from apoptotic death (and thereby exposing them to secondary events) or through cooperation with other oncogenes. The lack of reactivity in metastatic melanoma suggests that mechanisms other than Bcl-2 are involved in the survival and growth of metastatic melanoma cells.

[Acute hemorrhagic edema in an infant]. / Das akute hämorrhagische Odem beim Säugling.

The clinical and histological features of acute haemorrhagic oedema of childhood are discussed with reference to an actual case. Although closely related to Schoenlein-Henoch syndrome, it is considered a distinct entity, on the basis of the typical clinical picture and the excellent prognosis.

Acitretin as cancer chemoprophylaxis in a renal transplant recipient.

The use of acitretin in a renal transplant recipient who had been treated for several premalignant and malignant skin lesions is the subject of this case report. During the treatment period no new dysplastic lesions developed.