|
The skin barrier function is primarily located in the stratum corneum (SC) comprised of corneocytes and lipids The main lipid classes in the stratum corneum are ceramides, free fatty acids (FFAs), and cholesterol. These lipids form crystalline lipid lamellae. The composition and organization of these lipids are crucial for a proper skin barrier function, but the importance of the chain length distribution of the ceramides and FFAs for the impaired skin barrier is not known. We performed a clinical study in which the SC lipids and their importance for the skin barrier function was examined in atopic eczema patients and compared with control subjects. The lipid composition was examined with mass spectrometry. In particular the carbon chain length of the ceramides and FFAs was investigated in relation to the density of the SC lipid organization (examined by infrared spectroscopy) and the transepidermal water loss (TEWL), a marker for the skin permeability barrier. In addition we used lipid membrane studies to examine whether the changes observed in atopic dermatitis skin also results in an increased permeation across these membranes. In addition we examined whether inflammation that occurs in lesional AD skin could account for changes in lipid composition. This was done by supplementation culture medium of human skin equivalents with cytokines. A reduction was observed in the FFA and ceramide chain lengths for both non-lesional and lesional SC of AD patients compared to control skin. In lesional skin the reduction in chain length was more pronounced than in non-lesional skin(1). Furthermore, in lesional skin an increased level of unsaturated fatty acids was observed. The reduction in lipid chain length correlated excellent with a less dense lipid organization and a reduced skin barrier function. Besides, we examined the effect of mutations in the filaggrin gene on the lipids properties, a major predisposition factor for development of AD(2). However, no association was observed between lipid properties and filaggrin mutations. In order to examine whether the changes in lipid composition may be an important underlying factor for the reduced skin barrier in AD, we performed lipid membrane studies and showed that changes similar as observed in AD can account for on increased permeability of (model) drugs through these lipid membranes. In addition, we noticed that using human skin equivalents inflammation may induced changes in the lipid composition resulting in a compromised skin barrier. The current studies provides insights into the role of the SC lipid chain length and shows that the lipids play a role in the impaired skin barrier of AD patients. These results may provide opportunities for studies on skin barrier repair by topical treatments and shows evidence that normalisation of the lipid synthesis may enhance normalisation of the skin barrier function.
|