Depletion of stratum corneum intercellular lipid lamellae and barrier function abnormalities after long-term topical corticosteroids

1997 ◽  
Vol 136 (6) ◽  
pp. 884-890 ◽  
Author(s):  
H.-M. SHEU ◽  
J.Y.-Y. LEE ◽  
C.-Y. CHAI ◽  
K.-W. KUO
Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1649
Author(s):  
Johannes Schleusener ◽  
Andrew Salazar ◽  
Jörg von Hagen ◽  
Jürgen Lademann ◽  
Maxim E. Darvin

The influence of a topically applied formulation containing components of natural moisturizing factor (NMF) on barrier-related parameters of the stratum corneum (SC) was investigated in vivo using confocal Raman microspectroscopy in a randomized, placebo-controlled double-blind study on 12 volunteers for 14 days. This method allowed for the elucidation of subtle differences between the verum and the placebo even though the components of the verum naturally occur in the SC. This differentiation is not possible non-invasively by conventional methods. In this study, we found that the applied verum and placebo formulations disrupted the equilibrium of water, NMF and lipids in the SC. The adverse effects of the formulation could be mitigated by incorporating it into a simplified supplementation of NMF molecules. As a long-term effect, the amount of strongly bound water increases at 30–40% SC depth (p < 0.05) and the amount of weakly bound water decreases at 30–40% SC depth (p < 0.05) for the verum. This supplement was also unexpectedly able to prevent intercellular lipids (ICL) disorganization in selected depths. In the long term, the verum treatment limited the lateral disorganization of the ICL to the upper 20% SC depth. Further research is required to elucidate the interplay of these factors in the SC, to better understand their contribution to the equilibrium and barrier function of the skin. This understanding of the interaction of these naturally occurring components could help in the future to develop and optimize topical treatments for diseases like psoriasis, atopic dermatitis, ichthyosis where the skin barrier is disrupted.


The Analyst ◽  
2016 ◽  
Vol 141 (6) ◽  
pp. 1981-1987 ◽  
Author(s):  
ChunSik Choe ◽  
Jürgen Lademann ◽  
Maxim E. Darvin

The intercellular lipid structure of the stratum corneum (SC) plays a key role in skin barrier function.


2015 ◽  
Vol 47 (8) ◽  
pp. 355-363 ◽  
Author(s):  
Chisato Oba ◽  
Kyoko Ito ◽  
Satomi Ichikawa ◽  
Masashi Morifuji ◽  
Yuji Nakai ◽  
...  

Dietary collagen hydrolysate has been hypothesized to improve skin barrier function. To investigate the effect of long-term collagen hydrolysate administration on the skin, we evaluated stratum corneum water content and skin elasticity in intrinsically aged mice. Female hairless mice were fed a control diet or a collagen hydrolysate-containing diet for 12 wk. Stratum corneum water content and skin elasticity were gradually decreased in chronologically aged control mice. Intake of collagen hydrolysate significantly suppressed such changes. Moreover, we used DNA microarrays to analyze gene expression in the skin of mice that had been administered collagen hydrolysate. Twelve weeks after the start of collagen intake, no significant differences appeared in the gene expression profile compared with the control group. However, 1 wk after administration, 135 genes were upregulated and 448 genes were downregulated in the collagen group. This suggests that gene changes preceded changes of barrier function and elasticity. We focused on several genes correlated with functional changes in the skin. Gene Ontology terms related to epidermal cell development were significantly enriched in upregulated genes. These skin function-related genes had properties that facilitate epidermal production and differentiation while suppressing dermal degradation. In conclusion, our results suggest that altered gene expression at the early stages after collagen administration affects skin barrier function and mechanical properties. Long-term oral intake of collagen hydrolysate improves skin dysfunction by regulating genes related to production and maintenance of skin tissue.


Author(s):  
R. R. Warner

Keratinocytes undergo maturation during their transit through the viable layers of skin, and then abruptly transform into flattened, anuclear corneocytes that constitute the cellular component of the skin barrier, the stratum corneum (SC). The SC is generally considered to be homogeneous in its structure and barrier properties, and is often shown schematically as a featureless brick wall, the “bricks” being the corneocytes, the “mortar” being intercellular lipid. Previously we showed the outer SC was not homogeneous in its composition, but contained steep gradients of the physiological inorganic elements Na, K and Cl, likely originating from sweat salts. Here we show the innermost corneocytes in human skin are also heterogeneous in composition, undergoing systematic changes in intracellular element concentration during transit into the interior of the SC.Human skin biopsies were taken from the lower leg of individuals with both “good” and “dry” skin and plunge-frozen in a stirred, cooled isopentane/propane mixture.


2021 ◽  
pp. 1-13
Author(s):  
Philip W. Wertz

Cornified cells of the stratum corneum have a monolayer of an unusual lipid covalently attached to the outer surface. This is referred to as the corneocyte lipid envelope (CLE). It consists of a monolayer of ω-hydroxyceramides covalently attached to the outer surface of the cornified envelope. The CLE is essential for proper barrier function of the skin and is derived from linoleate-rich acylglucosylceramides synthesized in the viable epidermis. Biosynthesis of acylglucosylceramide and its conversion to the cornified envelope is complex. Acylglucosylceramide in the bounding membrane of the lamellar granule is the precursor of the CLE. The acylglucosylceramide in the limiting membrane of the lamellar granule may be oriented with the glucosyl moiety on the inside. Conversion of the acylglucosylceramide to the CLE requires removal of the glucose by action of a glucocerebrosidase. The ester-linked fatty acid may be removed by an as yet unidentified esterase, and the resulting ω-hydroxyceramide may become ester linked to the outer surface of the cornified envelope through action of transglutaminase 1. Prior to removal of ester-linked fatty acids, linoleate is oxidized to an epoxy alcohol through action of 2 lipoxygenases. This can be further oxidized to an epoxy-enone, which can spontaneously attach to the cornified envelope through Schiff’s base formation. Mutations of genes coding for enzymes involved in biosynthesis of the CLE result in ichthyosis, often accompanied by neurologic dysfunction. The CLE is recognized as essential for barrier function of skin, but many questions about details of this essentiality remain. What are the relative roles of the 2 mechanisms of lipid attachment? What is the orientation of acylglucosylceramide in the bounding membrane of lamellar granules? Some evidence supports a role for CLE as a scaffold upon which intercellular lamellae unfold, but other evidence does not support this role. There is also controversial evidence for a role in stratum corneum cohesion. Evidence is presented to suggest that covalently bound ω-hydroxyceramides serve as a reservoir for free sphingosine that can serve in communicating with the viable epidermis and act as a potent broad-acting antimicrobial at the skin surface. Many questions remain.


2021 ◽  
Vol 22 (2) ◽  
pp. 720
Author(s):  
Bin Zhang ◽  
Ruenn Chai Lai ◽  
Wei Kian Sim ◽  
Andre Boon Hwa Choo ◽  
Ellen Birgit Lane ◽  
...  

Severe psoriasis, a chronic inflammatory skin disease is increasingly being effectively managed by targeted immunotherapy but long-term immunotherapy poses health risk and loss of response. Therefore, there is a need for alternative therapy strategies. Mesenchymal stem/stromal cell (MSC) exosomes are widely known for their potent immunomodulatory properties. Here we investigated if topically applied MSC exosomes could alleviate psoriasis-associated inflammation. Topically applied fluorescent exosomes on human skin explants were confined primarily to the stratum corneum with <1% input fluorescence exiting the explant over a 24-h period. Nevertheless, topically applied MSC exosomes in a mouse model of imiquimod (IMQ) psoriasis significantly reduced IL-17 and terminal complement activation complex C5b-9 in the mouse skin. MSC exosomes were previously shown to inhibit complement activation, specifically C5b-9 complex formation through CD59. Infiltration of neutrophils into the stratum corneum is characteristic of psoriasis and neutrophils are a major cellular source of IL-17 in psoriasis through the release of neutrophil extracellular traps (NETs). We propose that topically applied MSC exosomes inhibit complement activation in the stratum corneum and this alleviates IL-17 release by NETS from neutrophils that accumulate in and beneath the stratum corneum.


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