Brn2 Is a Transcription Factor Regulating Keratinocyte Differentiation with a Possible Role in the Pathogenesis of Lichen Planus

Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Immunohistochemical analysis showed that Brn2 is expressed primarily in the upper granular layer. Consistent with its epidermal localization, Brn2 expression was highly induced at 14 days after calcium treatment of cultured normal human epidermal keratinocytes. When Brn2 was overexpressed by adenoviral transduction, Brn2 led to increased expression of the differentiation-related genes involucrin, filaggrin, and loricrin in addition to inhibition of their proliferation. Chromatin immunoprecipitation demonstrated that Brn2 bound to the promoter regions of these differentiation-related genes. We injected the purified Brn2 adenovirus into rat skin, which led to a thickened epidermis with increased amounts of differentiation related markers. The histopathologic features of adenovirus-Brn2 injected skin tissues looked similar to the features of lichen planus, a human skin disease showing chronic inflammation and well-differentiated epidermal changes. Moreover, Brn2 is shown to be expressed in almost all cell nuclei of the thickened epidermis of lichen planus, and Brn2 also attracts T lymphocytes. Our results demonstrate that Brn2 is probably a transcriptional factor playing an important role in keratinocyte differentiation and probably also in the pathogenesis of lichen planus lesions

Degradation of haloaromatic compounds

An ever increasing number of halogenated organic compounds has been produced by industry in the last few decades. These compounds are employed as biocides, for synthetic polymers, as solvents, and as synthetic intermediates. Production figures are often incomplete, and total production has frequently to be extrapolated from estimates for individual countries. Compounds of this type as a rule are highly persistent against biodegradation and belong, as "recalcitrant" chemicals, to the class of so-called xenobiotics. This term is used to characterise chemical substances which have no or limited structural analogy to natural compounds for which degradation pathways have evolved over billions of years. Xenobiotics frequently have some common features. e.g. high octanol/water partitioning coefficients and low water solubility which makes for a high accumulation ratio in the biosphere (bioaccumulation potential). Recalcitrant compounds therefore are found accumulated in mammals, especially in fat tissue, animal milk supplies and also in human milk. Highly sophisticated analytical techniques have been developed for the detection of organochlorines at the trace and ultratrace level

Oral lichen planus: Causes, diagnosis and management

Oral lichen planus (OLP) is a chronic inflammatory disease of unknown etiology. In this paper we review the clinical and histological features of OLP, process of OLP diagnosis, causes of OLP, management of OLP patients and medical treatment of OLP lesions. Approximately 0.2 per cent OLP patients develop intra-oral carcinoma each year compared with approximately 0.005 per cent Australian adults. Possible mechanisms of increased oral cancer risk in OLP patients are presented. The aims of current OLP therapy are to eliminate mucosal erythema and ulceration, alleviate symptoms and reduce the risk of oral cancer. Patient education may improve the outcomes of OLP therapy and further reduce the risk of oral cancer in OLP patients. Although OLP may be diagnosed clinically, appropriate specialist referral is required for: (i) histological diagnosis; (ii) assessment of causative/exacerbating factors, associated diseases and oral cancer risk; (iii) patient education and management; (iv) medical treatment; and (v) long-term review and re-biopsy as required