Expression of Caspase 14 and Filaggrin in Oral Squamous Carcinoma

Caspase 14 is one of the latter discovered members of the caspase enzyme family and, although sharing sequence homologies with the other caspases, it is not involved in apoptosis. Together with its co-factor filaggrin, it plays an important role in skin barrier formation. It is already known that caspase 14 proteins are reduced during neoplastic dedifferentiation in cervical intraepithelial neoplasms and in invasive cervical carcinomas. Oral squamous carcinoma tissues have not been systematically evaluated for caspase 14 expression yet. Formalin-fixed and paraffin-embedded samples from oral squamous carcinomas (n = 36 tumours from 34 patients), metastases (n = 15) and controls (leukoplakia, n = 10) were analysed by immunohistochemistry. In carcinomas, human papilloma virus (HPV) infection was tested by PCR. Here we demonstrate that, in oral epithelia, caspase 14 is expressed mainly by cells of the intermediate and superficial cell layers while filaggrin is expressed only in keratinising foci in leukoplakia. Caspase 14 and filaggrin are co-localised. In invasive oral carcinomas, reduced expression of caspase 14 was detectable in 47 % of tumours but was not associated with keratinisation, tumour differentiation or HPV infection. Filaggrin was detectable in a subfraction of tumours (56 %) and was restricted to keratinising areas of the carcinomas. In summary, in contrast to cervical carcinomas, partial loss of caspase 14 is not associated with dedifferentiation in neoplastic lesions of the oral mucosa or HPV infection.     

Filaggrin repeat number polymorphism is associated with a dry skin phenotype

Profilaggrin is a key epidermal protein, critical for the generation and maintenance of the stratum corneum barrier. It is encoded by a gene located in the epidermal differentiation complex of Chromosome 1q21 and is composed of multiple filaggrin repeats connected by highly conserved linker peptides. Within the human population the number of filaggrin repeats encoded by this gene varies between 10, 11 or 12 repeats. Using a PCR-based approach we have determined individual profilaggrin allelotypes in a group of 113 subjects and identified preliminary evidence of an inverse association between the 12 repeat allele and self-perceived frequent dry skin (P=0.0293). This is the first demonstration of a potential association between a genetic marker and cosmetic skin condition and suggests that cosmetic skin dryness may in part be genetically determined and associated with specific profilaggrin allelotypes.     

The content of free amino acids in the stratum corneum is increased in senile xerosis

Xerosis is one of the characteristics of aged skin. Xerosis may be caused by a decrease in the stratum corneum free amino acids which are natural moisturizing factors derived from filaggrin. In aged skin, filaggrin is immunohistochemically decreased compared with the levels in young skin. However, the differences in stratum corneum amino acids between aged and young skin have not been analyzed quantitatively. Therefore, in this study we determined the stratum corneum amino acids per 1000 stratum corneum cells in aged and young skin by high-performance liquid chromatography. The amount of filaggrin mRNA in the epidermis was also compared between aged and young skin using RT-PCR. The total amount of amino acids in the stratum corneum was larger in aged senile xerosis skin than in young skin. Only a few amino acids were found in the stratum corneum of ichthyosis vulgaris patients (control skin). The expression of filaggrin mRNA in aged skin was, however, similar to that in young skin. These findings suggest that the immunohistochemical decrease in filaggrin in aged skin may be caused by promotion of filaggrin proteolysis in the upper layers of the stratum spinulosum.     

From the outside-in: Epidermal targeting as a paradigm for atopic disease therapy

Atopic dermatitis(AD) is a chronic inflammatory skin disorder which can precede asthma and allergic rhinitis in a disease trajectory known as the atopic march. The pathophysiology of AD includes cutaneous inflammation, disrupted epidermal barrier function, xerosis and propensity to secondary infections. AD had previously been thought to arise from the systemic atopic immune response and therapies are therefore directed towards ameliorating Th2-mediated inflammation. However in recent years the focus has shifted towards primary defects in the skin barrier as an initiating event in AD. Links between loss-of-function variants in the gene encoding filaggrin and disrupted activity of epidermal serine proteases and AD have been reported. Based on these observations, a mechanism has been described by which epidermal barrier dysfunction may lead to inflammation and allergic sensitization. Exogenous and endogenous stressors can further exacerbate inherited barrier abnormalities to promote disease activity. Pathways underlying progression of the atopic march remain unclear, but recent findings implicate thymic stromal lymphopoietin as a factor linking AD to subsequent airway inflammation in asthma. This new appreciation of the epidermis in the development of AD should lead to deployment of more specific strategies to restore barrier function in atopic patients and potentially halt the atopic march.     

延边朝鲜族AD患者FLG基因SNPs与血清生化指标相关性分析

目的研究延边地区朝鲜族特应性皮炎患者丝聚蛋白基因单核苷酸多态性与血清IgE及IL-13相关性分析。方法选择70例特应性皮炎患者和90例正常对照人群作为研究对象,使用PCR法,研究丝聚蛋白基因2个SNPs位点(rs11584340及rs3126085)的基因型分布,并进行生化指标在各基因型间比较。结果延边朝鲜族特应性皮炎组血清IgE及IL-13水平显著高于正常组(P<0.01);rs11584340多态在特应性皮炎组内基因型AG有增高血清IgE趋势(P=0.05),但与IL-13不相关(P>0.05)。结论血清IgE及IL-13与延边朝鲜族人群特应性皮炎有明显相关性,是特应性皮炎的危险因素;延边朝鲜族特应性皮炎患者中rs11584340多态基因型AG有增加血清IgE趋势。