Squamous cell carcinoma keratinocytes isolated from patients with recessive dystrophic epidermolysis bullosa invade collagen-matrigel organotypic skin equivalents in an autonomous fashion

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The genetic architecture and population genetics of filaggrin-related atopic dermatitis

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Photocontact allergic and phototoxic studies of chlorproethazine

Background: Neuriplege (R) cream was available as a non-prescription medication in France until its withdrawal from the market by regulatory authorities in January 2007. Its active ingredient is the phenothiazine chlorproethazine (CPE). Before its withdrawal, we investigated the photocontact allergic and phototoxic potential of Neuriplege (R) cream and CPE. Methods: An in vitro phototoxic study was performed in HaCaT keratinocytes using the neutral red dye phototoxic assay. Phototoxicity and photocontact allergy were assessed in humans by photopatch testing. Results: In vitro, a 1 h incubation of keratinocytes with CPE was approximately 13 times as toxic to the cells in the presence of ultraviolet light compared with incubation with the drug alone. Of two healthy volunteers initially photopatch tested to Neuriplege (R) cream on the arm, one developed a phototoxic reaction. These two volunteers were then photopatch tested to Neuriplege (R) and CPE on the back with seven additional healthy volunteers. Both of the initial study volunteers experienced a photocontact allergic reaction to Neuriplege (R) as is upon this re-exposure. Of the seven volunteers not previously exposed to Neuriplege (R) as is, five developed phototoxic reactions. Conclusions: This study demonstrates the strong phototoxic and photocontact allergic potential of CPE in Neuriplege (R) cream, and supports the decision of the French pharmaceutical regulatory authorities to withdraw it.</p

Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis

Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal-dominant disorder associated with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPLCA has been mapped to 5p13.1–q11.2, and by candidate gene analysis, we identified missense mutations in the OSMR gene, encoding oncostatin M-specific receptor β (OSMRβ), in three families. OSMRβ is a component of the oncostatin M (OSM) type II receptor and the interleukin (IL)-31 receptor, and cultured FPLCA keratinocytes showed reduced activation of Jak/STAT, MAPK, and PI3K/Akt pathways after OSM or IL-31 cytokine stimulation. The pathogenic amino acid substitutions are located within the extracellular fibronectin type III-like (FNIII) domains, regions critical for receptor dimerization and function. OSM and IL-31 signaling have been implicated in keratinocyte cell proliferation, differentiation, apoptosis, and inflammation, but our OSMR data in individuals with FPLCA represent the first human germline mutations in this cytokine receptor complex and provide new insight into mechanisms of skin itching