Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier

Jensen, Jens‐Michael; Schütze, Stefan; Förl, Michael; Krönke, Martin; Proksch, Ehrhardt

doi:10.1172/jci5307

Cited by 163 publications

(173 citation statements)

References 58 publications

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“…All diagrams in comparison show acidity increasing initially at the surface, which peaks at day 4, and in parallel, but separately increasing acidity at the SC/SG interface, which by day 4 forms a continuously spreading extracellular acidic pH domain (panels C), while pH distribution inside-out dominates thereafter (panels D). less active when SC is exposed to a neutral pH (Mauro et al, 1998), consistent with their known acidic pH optima (Jensen et al, 1999;Takagi et al, 1999;Schmuth et al 2000). Clearly, such correlations within localized domains are not possible with standard flat electrodes, which measure only surface pH.…”

Section: Discussionmentioning

confidence: 88%

“…Two of the ''lysosomal-type'' enzymes that are required for this lipid processing, b-glucocerebrosidase (b-GlcCer'-ase) and acidic sphingomyelinase (aSM'ase), are cosecrcted with the lipids to the extracellular domains of the lower SC, but both require an acidic milieu for optimal activity (Holleran et al, 1992;Jensen et al, 1999). Despite normal basal barrier function at birth (Cunico et al, 1977), even full-term infants' skin exhibits a greater tendency to develop irritant/allergic contact dermatitis when exposed to alkaline or neutral solutions (Wilhelm and Maibach, 1990;Berg et al, 1994;Seidenari and Giusti, 1995), suggesting that barrier function is not fully mature at birth.…”

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confidence: 99%

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Neonatal Development of the Stratum Corneum pH Gradient: Localization and Mechanisms Leading to Emergence of Optimal Barrier Function

et al. 2003

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 99%

Neonatal Development of the Stratum Corneum pH Gradient: Localization and Mechanisms Leading to Emergence of Optimal Barrier Function

et al. 2003

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“…Previous studies demonstrate that initial lipid processing normally occurs in extracellular domains (3), and that it is this initial lipid processing step, at the SG-SC interface and in the lower SC, that is disturbed in: 1) neutral buffer-exposed skin, 2) NHE1 Ϫ/Ϫ mice, and 3) normal mice treated with the specific NHE1 inhibitor, HOE694. This view is supported by insights from other knockout models/ diseases, which also reveal the SG-SC interface to be an area of intense enzymatic lipid processing activity (5)(6)(7)32). Here we show with FLIM that this compartment is already acidified in normal skin, contrary to the conventional view of the pH gradient obtained with flat electrodes, which would predict this compartment to be neutral.…”

Section: Nhe1 Regulates Epidermal Ph and Barrier Functionmentioning

confidence: 80%

“…The delay in recovery at a neutral pH is explained by the in situ activity profiles of ␤-glucocerebrosidase (␤-Glc-Cer'ase), and acidsphingomyelinase (aSM'ase) in the SC, which lack activity at a neutral pH (4,5). ␤-Glc-Cer'ase and aSM'ase comprise two key lipid hydrolases, which are critical for the formation of mature extracellular lamellar bilayers (6,7), and both are required for the normal processing of secreted polar lipid precursors into their more non-polar species.…”

mentioning

confidence: 99%

NHE1 Regulates the Stratum Corneum Permeability Barrier Homeostasis

Behne

Meyer

Hanson

et al. 2002

Journal of Biological Chemistry

190

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The outermost epidermal layer, the stratum corneum (SC), exhibits an acidic surface pH, whereas the pH at its base approaches neutrality. NHE1 is the only Na ؉ /H ؉ antiporter isoform in keratinocytes and epidermis, and has been shown to regulate intracellular pH. We now demonstrate a novel function for NHE1, as we find that it also controls acidification of extracellular "microdomains" in the SC that are essential for activation of pH-sensitive enzymes and the formation of the epidermal permeability barrier. NHE1 expression in epidermis is most pronounced in granular cell layers, and although the surface pH of NHE1 knockout mice is only slightly more alkaline than normal using conventional pH measurements, a more sensitive method, fluorescence lifetime imaging, demonstrates that the acidic intercellular domains at the surface and of the lower SC disappear in NHE1 ؊/؊ animals. Fluorescence lifetime imaging studies also reveal that SC acidification does not occur through a uniform gradient, but through the progressive accumulation of acidic microdomains. These findings not only visualize the spatial distribution of the SC pH gradient, but also demonstrate a role for NHE1 in the generation of acidic extracellular domains of the lower SC, thus providing the acidification of deep SC interstices necessary for lipid processing and barrier homeostasis.

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“…20 SMases are also important in maintaining the barrier function, and of various SMases, deficiency of aSMase has been reported to lead to epidermal barrier defects. 21,22 To further determine the contributions of GlcCer and SM hydrolysis in altering levels of Cer species, the activity of b-GlcCer'ase and aSMase was evaluated (Fig. 2).…”

Section: Activities and Protein Expressions Of B-glccer'ase And Asmasmentioning

confidence: 99%

Gromwell (Lithospermum erythrorhizon) Supplementation Enhances Epidermal Levels of Ceramides, Glucosylceramides, β-Glucocerebrosidase, and Acidic Sphingomyelinase in NC/Nga Mice

Kim

Cho

2013

Journal of Medicinal Food

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We have previously reported that dietary gromwell (Lithospermum erythrorhizon; LE) prevents the development of atopic dermatitis (AD) with increased epidermal levels of total ceramide (Cer), the major lipid maintaining epidermal barrier. In this study, we investigated whether the increased level of total Cer induced by dietary LE would be related to the altered metabolism of glucosylceramide (GlcCer) and sphingomyelin (SM), two major precursor lipids in Cer generation. NC/Nga mice, an animal model of AD, were fed a control diet (group CA: atopic control) or a diet with 70% ethanol LE extracts (1% in diet; group LE) for 10 weeks. Individual species of Cer, GlcCer, and SM were analyzed by highperformance thin layer chromatography. In the epidermis of group CA, total Cer (including Cer2 and Cer5-7) and total GlcCer (including GlcCer-B/C/D) were significantly reduced; these levels in group LE were increased to levels similar to the normal control group of BALB/c mice (group C). In addition, protein expressions and activities of b-glucocerebrosidase (b-GlcCer'ase) and acidic sphingomyelinase (aSMase), enzymes for GlcCer or SM hydrolysis, respectively, were increased in group LE. However, alterations of Cer1, Cer3/4, GlcCer-A, and all SM species (including SM1-3) were not significant among groups C, CA, and LE. Dietary gromwell increases GlcCer-B/C/D, and further enhances the generation of Cer2 and Cer5-7 with high protein expressions and activities of b-GlcCer'ase and aSMase.

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Roles for tumor necrosis factor receptor p55 and sphingomyelinase in repairing the cutaneous permeability barrier

Cited by 163 publications

References 58 publications

Neonatal Development of the Stratum Corneum pH Gradient: Localization and Mechanisms Leading to Emergence of Optimal Barrier Function

Neonatal Development of the Stratum Corneum pH Gradient: Localization and Mechanisms Leading to Emergence of Optimal Barrier Function

NHE1 Regulates the Stratum Corneum Permeability Barrier Homeostasis

Gromwell (Lithospermum erythrorhizon) Supplementation Enhances Epidermal Levels of Ceramides, Glucosylceramides, β-Glucocerebrosidase, and Acidic Sphingomyelinase in NC/Nga Mice

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