The stratum corneum, which is the outermost layer of the skin, functions as an important barrier to maintain biological homeostasis. The multilamellar structures formed by intercellular lipids present in the stratum corneum are considered to play an important role in barrier function. Most intercellular lipids are unbound and can be extracted by organic solvents, but some intercellular lipids are covalently bound to cornified envelope proteins. Decreases in unbound lipid levels reduce the barrier function of the stratum corneum, but the relationship between bound lipid and the barrier function of the stratum corneum is not well understood. In this study, we examined the relationship between the amount of covalently bound ceramide, the main bound lipid, and the barrier function of the stratum corneum. A single dose of UVB irradiation (2 x MED), or continuous UVB irradiation (0.5 x MED/day for 14 days) to the back, or feeding with an essential fatty acid-deficient (EFAD) diet for 8 weeks caused a significant elevation of TEWL and a significant reduction in covalently bound ceramides in hairless rats. Transmission electron microscopy revealed that the intercellular multilamellar structures in the stratum corneum of treated rats were incomplete (folding, defects, unclear images) compared to the structures seen in the stratum corneum of non-UVB-irradiated and non-EFAD rats. These results suggest that the amount of covalently bound ceramides is highly correlated with the barrier function of the skin, and that covalently bound ceramides play an important role in the formation of lamellar structures, and are involved in the maintenance of the barrier function of the skin.

Stratum corneum (SC) lipids are of particular importance in maintaining the permeability barrier function. Although many studies have demonstrated that UVB irradiation of mammalian skin reduces barrier function, the responsible alterations in SC lipid profiles are not known. In this study, we investigated both compositional and morphological alterations in SC lipids with the development of barrier abnormalities caused by daily UVB irradiation in hairless rat skin. The UVB irradiation of suberythemal doses (0.5 minimal erythema dose) significantly increased transepidermal water loss (TEWL) relative to nonirradiated control, indicating a diminished barrier function. Under these conditions, the total amounts of major SC lipid species (ceramides, cholesterol, free fatty acids) in UVB-irradiated SC did not differ from those in nonirradiated SC. However, electron microscopic observations revealed marked abnormalities in the intercellular domains of UVB-irradiated SC, where naturally occurring intercellular multilamellar structures were often absent and leaving the area with the appearance of an empty space. Moreover, in UVB-irradiated SC, individual corneocytes often showed small amounts of intercellular deposition product with abnormal lamellar structure, where lamellar body sphingomyelinase activity was present. These observations demonstrated a partial failure of lamellar body secretion in UVB-irradiated SC and suggested that a defect in the secretion of lamellar body-derived lipids and enzymes to SC intercellular space is, at least in part, responsible for the observed abnormal intercellular structure and barrier disruption.

Psoriasis is a chronic inflammatory skin disease developed under the influence of the IL-23/ Th17 axis and characterized by intense inflammation, as well as prominent epidermal hyperplasia. Here, we demonstrated that expression of galectin-8, a galactoside-binding lectin, was upregulated in the epidermis of human psoriatic skin lesions and the IL-23-induced mouse model. Meanwhile, galectin-8 knocked out mice showed a less prominent keratinocyte proliferation after intradermal IL-23 treatment. We also showed that IL-17A induced galectin-8 expression in human immortalized keratinocytes, HaCaT cells, and primary human keratinocytes, HEKn cells. In addition, we found that galectin-8 levels in keratinocytes were positively correlated with the proliferation ability of the cells. Furthermore, galectin-8 knocked out HaCaT cells showed a delay in transition from mitosis into G1 phase after cell cycle synchronization and release. The localization of galectin-8 within the mitotic apparatus was demonstrated by immunofluorescence staining and immunoblotting. Alpha-tubulin was one of the interacting proteins of galectin-8 during mitosis, as identified by co-immunoprecipitation and mass spectrometry analysis. In the absence of galectin-8, pericentrin compactness and mitotic tubule length were impaired as demonstrated by immunofluorescence staining. We conclude galectin-8 is upregulated in psoriasis and contributes to the hyperproliferation of keratinocytes by regulating mitosis through interacting with a-tubulin.