The stratum corneum as a protective biological membrane of the skin

The primary function of the epidermis is to produce the stratum corneum (SC), a barrier membrane on the skin surface, to protect our body from desiccation and at the same time to prevent invasion by injurious exogenous agents. The intercellular lipids, particularly ceramides, derived from lamellar bodies, play an important role in the barrier function of the SC. The water barrier function of the SC can be evaluated by measurement of the transepidermal water loss (TEWL). The SC can also bind water to keep the skin surface soft and smooth. This water-holding capacity depends on the presence of both the intercellular lipids and water-soluble amino acids in the SC, Particularly the latter are deficient in pathological SC. The superficial portion of the SC easily develops firm and brittle skin surface changes whenever its hydration state is reduced due to a functional deficiency of the SC that makes it unable to retain enough water even in usual ambient conditions. The hydration state of the skin surface can be quickly and accurately evaluated noninvasively by measuring the high-frequency conductance values of the skin. A reduced hydration state can be alleviated by topical application of Various moisturizers. Based on the results of simultaneous measurements of TEWL and high-frequency conductance, we can classify the SC into three functional types. The first is the most commonly observed pattern in which the SC shows decreases in both the water-holding capacity and water barrier function demonstrable by high levels of TEWL, as observed in various scary inflammatory lesions. Another is noted as an increase in the hydration state of the SC accompanied by increased water loss as demonstrated in fresh scars, hypertrophic scars and keloids, as well as in retinoid-treated skin. The last type is a poorly hydrated SC surface associated with a decrease in TEWL as observed in senile xerosis. Lastly, the SC exerts an explosive proinflammatory effect when it is placed in living tissues as in acne, ruptured epidermal cysts, ingrown nails and pseudofolliculitis barbae, in addition to various sterile subcorneal pustules in which the SC is directly exposed to tissue fluids. The SC activates complement through the alternative pathway to generate proinflammatory C5a anaphylatoxin. Moreover, upon activation of the complement, the type 3 complement receptor (CR3 or Mac-1; CD11b/CD18) functions as an opsonic receptor, promoting the binding of neutrophils which generate reactive oxygen species to further damage the surrounding tissue. The early neutrophil-dominated inflammation is followed by the accumulation of monocytes to produce SC-induced granuloma. Activated neutrophils release monocyte chemotactic factors, which partly consist of chemokines such as MIP-1 alpha, MIP-1 beta and MCP-1, in addition to unidentified factors with Ear higher molecular weight values. The epidermal cells, particularly the well differentiated ones located in the upper portion, secrete key biologically active substances of the complement system, i.e., C3 and factor B, to facilitate the SC-induced complement-activation in addition to the secretion of various proinflammatory modulators including cytokines, such as interleukin (IL)-1 alpha, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and granulocyte-macrophage colony-stimulating factor (GMCSF). The presence of proinflammatory cytokines such as INF gamma and TNF alpha in inflamed skin synergistically augment the C3 production by epidermal keratinocytes. The SC is a very rich reservoir of porinflamatory cytokine IL-1 and well hydrated SC releases IL-1 alpha time-dependently Thus, prolonged occlusion of the skin induces hydration dermatitis. The SC also contains a physiological antagonist, IL-1 receptor antagonist (IL-1RA), which competes with the binding of IL-1 to the IL-1 receptor, is produced in various types of inflamed skin, probably to modulate the intensity of inflammation.