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Notes: Summary Background Caveolin-1 is a key structural and functional protein for plasmalemmal invaginations termed caveolae. Caveolin-1 is known to modulate multiple signal-transducing pathways involved in cell differentiation and proliferation. Psoriasis is viewed as a multifactorial pathology characterized by keratinocyte hyperproliferation and abnormal cell maturation. We hypothesized that loss of caveolin-1 within epidermal keratinocytes may contribute to the development and/or progression of the psoriatic phenotype. Objectives To examine the expression and spatial distribution of caveolin-1 in skin biopsies from normal subjects and in patients with psoriasis. Methods Using immunohistochemical methods caveolin-1 protein expression was assayed in two independent patient groups. Firstly, a retrospective analysis was conducted on archival skin samples obtained from nine normal subjects and from involved tissue of 12 patients with psoriasis. Following this, a prospectively designed study was conducted in 10 further patients with active psoriasis and involving caveolin-1 staining of biopsy tissue from the uninvolved, advancing edge and lesional skin tissue from within the same subject. Results In normal skin or uninvolved skin from psoriasis patients intense caveolin-1 staining was present throughout full-thickness epidermis. In 20 of the 22 patient cases (combined retrospective and prospective samples) caveolin-1 protein was significantly reduced and consistently showed very weak or absent staining within the hyperproliferative basal cell layers of the psoriatic plaque (P 〈 0·002 for retrospective archival study and P 〈 0·01 for prospectively designed study). Comparisons between caveolin-1 staining in uninvolved tissue and at the advancing edge of a migrating plaque were more equivocal (P 〉 0·05). Conclusions The findings of this study are consistent with a downregulation of caveolin-1 that may serve as an aetiological factor in the development and/or progression of psoriasis. Further mechanistic investigations are required with the potential that caveolin-1 protein may be a novel target for therapy of psoriasis.

Notes: Background Despite the benefits of mercury-containing amalgam dental fillings there are growing concerns regarding the potential adverse health effects arising from exposure to mercury released from fillings. In some individuals this process may result in a local lichenoid reaction of the oral mucosa. Objectives The aim of this study was to investigate the possibility that mercury salts released from amalgam fillings might act directly on oral keratinocytes to induce changes that could promote the development of such lesions. Methods In vitro experiments were performed in which normal oral and cutaneous keratinocytes were cultured in the presence of mercuric chloride (HgCl2). ICAM-1 expression and the release of cytokines was determined by enzyme-linked immunosorbent assay techniques. T-cell binding to HgCl2-pretreated keratinocytes was assessed using a colorimetric method. Results Subcytotoxic concentrations of HgCl2 induced a concentration-related increase in ICAM-1 expression and consequent T-cell binding on oral, but not cutaneous, keratinocytes. HgCl2 also stimulated the release of low levels of tumour necrosis factor-α and interleukin-8 (but not RANTES), and inhibited the release of interleukin-1α by oral keratinocytes. Conclusions This study provides evidence that oral keratinocytes may play an integral part in initiating the pathogenesis of amalgam-induced lichenoid reactions.

Notes: Chronically sun-exposed or photodamaged human skin is characterized by a number of clinical features, including wrinkles. However, little is known about the molecular mechanisms that underlie these features. We investigated the hypothesis that the mechanism of wrinkle formation may involve loss of anchoring fibrils, composed mainly of collagen VII, which are important in maintaining dermal-epidermal junction integrity. Ten volunteers with moderate to severe photodamage of dorsal forearm skin were recruited to the study. Using immunohistochemistry, transmission electron microscopy and in situ hybridization, we compared collagen VII protein and mRNA content of photodamaged forearm skin with that of sun-protected hip and upper inner arm skin from the same subjects. Numbers of anchoring fibrils per linear μm of basement membrane (mean ± SEM) were significantly lower in photodamaged skin (1·79±0·10) as compared with sun-protected hip (2·28±0·11) and upper inner arm skin (2·21±0·10) (P〈0·01), and similarly keratinocyte expression of collagen VII mRNA, quantitated as number of positively stained keratinocytes per high power field, was significantly reduced in photodamaged skin (6·3±2·5) as compared with sunprotected hip (20·0±5·6) and upper inner arm skin (17·7±4·9) (P〈0·001). Semiquantitative assessment of immunohistochemical staining for collagen VII showed a non-significant reduction in photodamaged skin as compared with sun-protected skin. We propose that reduced content of collagen VII in photodamaged skin contributes to wrinkle formation by weakening the bond between the dermis and epidermis.

Notes: Background Several of the characteristic clinical features of photoaged skin, including wrinkling, are thought to be dependent on changes in the dermal matrix brought about by chronic sun exposure. Such changes include reductions in collagens I, III and VII, an increase in elastotic material in the reticular dermis and a marked reduction in the microfibrillar glycoprotein fibrillin. Objectives To examine whether type VI collagen, a microfibrillar collagen necessary for cell–cell and cell–matrix communication, is affected by the photoageing process. Methods Six healthy volunteers with moderate to severe photoageing were enrolled into the study. Immunohistochemistry and in situ hybridization histochemistry were used to examine the levels of type VI collagen in photoprotected and photoaged sites. Results In photoprotected skin, type VI collagen was concentrated in the papillary dermis immediately below the dermal–epidermal junction, around blood vessels, hair follicles and glandular structures. The distribution of type VI collagen was unchanged in photoaged skin, although we observed an increase in the abundance of the α3 chain of collagen VI in the upper papillary dermis, at its junction with the dermal–epidermal junction (P 〈 0·05). No alterations were observed for any α chain at the mRNA level. Conclusions These studies suggest that chronic sun exposure (photoageing) has little or no effect on either the distribution, abundance or levels of expression of type VI collagen in human skin. Thus, type VI collagen, unlike other matrix components so far studied, appears to be relatively unaffected by the photoageing process.