An Update of the Defensive Barrier Function of Skin

Skin, as the outermost organ in the human body, continuously confronts the external environment and serves as a primary defense system. The protective functions of skin include UV-protection, anti-oxidant and antimicrobial functions. In addition to these protections, skin also acts as a sensory organ and the primary regulator of body temperature. Within these important functions, the epidermal permeability barrier, which controls the transcutaneous movement of water and other electrolytes, is probably the most important. This permeability barrier resides in the stratum corneum, a resilient layer composed of corneocytes and stratum corneum intercellular lipids. Since the first realization of the structural and biochemical diversities involved in the stratum corneum, a tremendous amount of work has been performed to elucidate its roles and functions in the skin, and in humans in general. The perturbation of the epidermal permeability barrier, previously speculated to be just a symptom involved in skin diseases, is currently considered to be a primary pathophysiologic factor for many skin diseases. In addition, much of the evidence provides support for the idea that various protective functions in the skin are closely related or even co-regulated. In this review, the recent achievements of skin researchers focusing on the functions of the epidermal permeability barrier and their importance in skin disease, such as atopic dermatitis and psoriasis, are introduced.

An Update of the Defensive Barrier Function of Skin

Skin, as the outermost organ in the human body, continuously confronts the external environment and serves as a primary defense system. The protective functions of skin include UV-protection, anti-oxidant and antimicrobial functions. In addition to these protections, skin also acts as a sensory organ and the primary regulator of body temperature. Within these important functions, the epidermal permeability barrier, which controls the transcutaneous movement of water and other electrolytes, is probably the most important. This permeability barrier resides in the stratum corneum, a resilient layer composed of corneocytes and stratum corneum intercellular lipids. Since the first realization of the structural and biochemical diversities involved in the stratum corneum, a tremendous amount of work has been performed to elucidate its roles and functions in the skin, and in humans in general. The perturbation of the epidermal permeability barrier, previously speculated to be just a symptom involved in skin diseases, is currently considered to be a primary pathophysiologic factor for many skin diseases. In addition, much of the evidence provides support for the idea that various protective functions in the skin are closely related or even co-regulated. In this review, the recent achievements of skin researchers focusing on the functions of the epidermal permeability barrier and their importance in skin disease, such as atopic dermatitis and psoriasis, are introduced.

Epidermal Barrier in Human Fetus and Newborn / 대한피부과학회지

BACKGROUND: The lipids of the stratum corneum, which originate from polar lipid precursors provided by the cells of the stratum granulosum via the exocytosis of lamellar bodies, with cornified cell envelope form competent epidermal barrier structurally and functionally. The ontogeny of the epidermal barrier is not clearly defined because of difficulty of sampling and methodology which defines epidermal lipids. OBJECT: From ultrastructural observation of skin samples obtained from human fetuses and newborn on serial developmental timings, we tried to clarify the sequential development of epidermal barrier. METHODS: Skin samples were obtained from 13 human fetuses from EGA(estimated gestational age) 10 to 23wks and 2 newborns. Specimens were observed by fluorescent confocal microscopy with nile red to identify the distribution of epidermal lipids, by transmission electron microscope with lanthanum to investigate the functional permeability barrier, with RuO4 to observe the intercellular lipid bilayer and morphology of lamellar bodies, with ion capture cytochemistry to investigate the formation of epidermal calcium gradient. RESULT: In nile red stain, the amount of epidermal lipid increased during fetal period. At EGA 23wks, the lipid distribution revealed linear and continuous pattern. In lanthanum tracer study, the electron dense tracer permeated all the intercellular space of the epidermis up to periderm and subepidermal space until EGA 21wks. At EGA 23wks, the tracer permeated intercellular space of epidermis weakly. It might be predicted that incomplete epidermal barrier is present at this time. In RuO4 stain, precursor of lamellar body was observed at EGA 15wks, and intercellular lipid bilayer was observed at EGA 16wks. As gestation increases, there was a steady increase in epidermal lipid bilayers. In ion capture cytochemistry, epidermal calcium gradient was first observed in follicular epidermis at EGA 20wks, and in interfollicular epidermis at EGA 23wks. From these results, it is concluded that the basic structures of epidermal barrier are formed at EGA 23wks, but it is not complete, and epidermal barrier arises first from follicular epidermis.

The Effects of Change in Epidermal Calcium Gradient on Keratinocyte Differentiation / 대한피부과학회지

BACKGROUND: The cornified cell envelope(CE) which is formed during the terminal differentiation of keratinocytes, is a specialized structure which forms a structurally and functionally complete permeability barrier. OBJECTIVE: The purpose of our study is to investigate the effects of changes in the calcium ions on keratinocyte differentiation, especially in the expression of CE protein. METHODS:The permeability barrier of hairless mice was disrupted by tape-stripping and then exposed to the air or occluded with a water-vapor impermeable membrane, and iontophoresis was done without permeability barrier perturbation. Skin specimens were prepared for ion capture cytochemistry and immunohistochemistry with anti-K5, anti-K10, anti-K6, anti-involucrin and anti-loricrin. RESULTS: The calcium gradient which disappeared after tape-stripping was restored at 36 h after tape-stripping with air exposure and at 60 h after tape-stripping with occlusion. The change in calcium ions produced by both positive and negative iontophoresis showed recovery at 6 h. Expression of basal K5 showed a slight decrease and expression of suprabasal K10 showed an increase at 12 h with air exposure after tape-stripping, tape stripping with occlusion, and iontophoresis. Expression of K6 appeared at 12 h after tape-stripping and then in the whole epidermis at 36 h with air exposure after tape-stripping and tape stripping with occlusion and focally appeared in the stratum granulosum and stratum spinosum after iontophoresis. Expression of involucrin was increased at 12 h with air exposure after tape-stripping and iontophoresis and was extended to the lower spinous layers in tape-stripping with occlusion. Expression of loricrin in air exposure after tape-stripping, tape-stripping with occlusion and iontophoresis was similar to that of normal skin. CONCLUSION: The changes in calcium ions without permeability barrier perturbation are related to the expression of CE protein. It is thought that calcium ions in the epidermis have an important role in the terminal differentiation of keratinocytes.

The Effects of Change in Epidermal Calcium Gradient on Keratinocyte Differentiation / 대한피부과학회지

BACKGROUND: The cornified cell envelope(CE) which is formed during the terminal differentiation of keratinocytes, is a specialized structure which forms a structurally and functionally complete permeability barrier. OBJECTIVE: The purpose of our study is to investigate the effects of changes in the calcium ions on keratinocyte differentiation, especially in the expression of CE protein. METHODS:The permeability barrier of hairless mice was disrupted by tape-stripping and then exposed to the air or occluded with a water-vapor impermeable membrane, and iontophoresis was done without permeability barrier perturbation. Skin specimens were prepared for ion capture cytochemistry and immunohistochemistry with anti-K5, anti-K10, anti-K6, anti-involucrin and anti-loricrin. RESULTS: The calcium gradient which disappeared after tape-stripping was restored at 36 h after tape-stripping with air exposure and at 60 h after tape-stripping with occlusion. The change in calcium ions produced by both positive and negative iontophoresis showed recovery at 6 h. Expression of basal K5 showed a slight decrease and expression of suprabasal K10 showed an increase at 12 h with air exposure after tape-stripping, tape stripping with occlusion, and iontophoresis. Expression of K6 appeared at 12 h after tape-stripping and then in the whole epidermis at 36 h with air exposure after tape-stripping and tape stripping with occlusion and focally appeared in the stratum granulosum and stratum spinosum after iontophoresis. Expression of involucrin was increased at 12 h with air exposure after tape-stripping and iontophoresis and was extended to the lower spinous layers in tape-stripping with occlusion. Expression of loricrin in air exposure after tape-stripping, tape-stripping with occlusion and iontophoresis was similar to that of normal skin. CONCLUSION: The changes in calcium ions without permeability barrier perturbation are related to the expression of CE protein. It is thought that calcium ions in the epidermis have an important role in the terminal differentiation of keratinocytes.