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Peter M. Elias - One of the best experts on this subject based on the ideXlab platform.

  • ph directly regulates epidermal permeability barrier homeostasis and Stratum Corneum integrity cohesion
    Journal of Investigative Dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (<20 min) of serine proteases, assessed by in situ zymography, followed by serine-protease-mediated degradation of corneodesmosomes. Western blotting revealed degradation of desmoglein 1, a key corneodesmosome structural protein, in parallel with loss of corneodesmosomes. Coapplication of serine protease inhibitors with the superbase normalized Stratum Corneum integrity/cohesion. The superbases also delayed permeability barrier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, resulting in a lipid-processing defect on electron microscopy. These studies demonstrate unequivocally that Stratum Corneum neutralization alone provokes Stratum Corneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased Stratum Corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.

  • glycerol regulates Stratum Corneum hydration in sebaceous gland deficient asebia mice
    Journal of Investigative Dermatology, 2003
    Co-Authors: Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Philip W. Wertz, Man Maoqiang, John P Sundberg, Peter M. Elias
    Abstract:

    The only known function of human sebaceous glands is the provocation of acne. We assessed here whether sebum influences Stratum Corneum hydration or permeability barrier function in asebia J1 and 2 J mice, with profound sebaceous gland hypoplasia. Asebia J1 mice showed normal permeability barrier homeostasis and extracellular lamellar membrane structures, but they displayed epidermal hyperplasia, inflammation, and decreased (>50%) Stratum Corneum hydration, associated with a reduction in sebaceous gland lipids (wax diesters/monoesters, sterol esters). The triglyceride content of both asebia and control Stratum Corneum was low, consistent with high rates of triglyceride hydrolysis within the normal pilosebaceous apparatus, despite high rates of triglyceride synthesis. Although a mixture of synthetic, sebum-like lipids (sterol/wax esters, triglycerides) did not restore normal Stratum Corneum hydration to asebia skin, topical glycerol, the putative product of triglyceride hydrolysis in sebaceous glands, normalized Stratum Corneum hydration, and the glycerol content of asebia Stratum Corneum was 85% lower than in normal Stratum Corneum. In contrast, another potent endogenous humectant (urea) did not correct the abnormality. The importance of glycerol generation from triglyceride in sebaceous glands for Stratum Corneum hydration was demonstrated further by (i) the absence of sebaceous-gland-associated lipase activity in asebia mice, whereas abundant enzyme activity was present in the glands of control mice; and (ii) the inability of high concentrations of topical triglyceride to correct the hydration abnormality, despite the presence of abundant lipase activity in asebia Stratum Corneum. These results show that sebaceous-gland-derived glycerol is a major contributor to Stratum Corneum hydration.

  • pH directly regulates epidermal permeability barrier homeostasis, and Stratum Corneum integrity/cohesion.
    The Journal of investigative dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (

  • generation of free fatty acids from phospholipids regulates Stratum Corneum acidification and integrity
    Journal of Investigative Dermatology, 2001
    Co-Authors: Joachim W Fluhr, Peter M. Elias, Kenneth R. Feingold, Mahendra Kumar Jain
    Abstract:

    There is evidence that the "acid mantle" of the Stratum Corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the Stratum Corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to Stratum Corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA 2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered Stratum Corneum integrity (number of strippings required to break the barrier) and decreased Stratum Corneum cohesion (protein weight removed per stripping). Not only Stratum Corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine Stratum Corneum to a neutral pH for as little as 3 h produced comparable abnormalities in Stratum Corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in Stratum Corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the Stratum Corneum (shown by immunofluorescence staining and vizualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal Stratum Corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of Stratum Corneum integrity and cohesion.

  • The biochemistry and function of Stratum Corneum lipids.
    Advances in lipid research, 1991
    Co-Authors: Nanna Y. Schürer, Peter M. Elias
    Abstract:

    Publisher Summary This chapter discusses the biochemistry and function of Stratum Corneum lipids. The study of lipids as a class of chemical constituents of the Stratum Corneum offers a unique opportunity to investigate the functional specialization of this tissue. The daily rate of epidermal lipid synthesis in man is equal to the lipid content times the daily loss of Stratum Corneum. Total epidermal lipid constitutes approximately 10–14% of the dry weight of mammalian epidermis. However, by themselves, isolated intercellular lipids possess no water-holding capacity. The ability of the intercellular lipids to form lamellar bilayers, in the absence of phospholipids, is dependent upon the amphipathic properties of ceramides, free fatty acids, cholesterol, and perhaps lesser constituents such as cholesterol sulfate and proteolipids. The lamellar bilayers are stabilized in an aqueous environment by van der Waals interactions and hydrogen bonds. Moreover, recently, it has been suggested that a major component of the Stratum Corneum is a ceramide, consisting of 30 to 34-carbon chain length, N-acyl, ω-hydroxyacids covalently bound to the cornified envelope. This leaflet may serve as a scaffold for the intercellular bilayers, thereby contributing to both the barrier and the cohesive properties of the Stratum Corneum.

Joachim W Fluhr - One of the best experts on this subject based on the ideXlab platform.

  • ph directly regulates epidermal permeability barrier homeostasis and Stratum Corneum integrity cohesion
    Journal of Investigative Dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (<20 min) of serine proteases, assessed by in situ zymography, followed by serine-protease-mediated degradation of corneodesmosomes. Western blotting revealed degradation of desmoglein 1, a key corneodesmosome structural protein, in parallel with loss of corneodesmosomes. Coapplication of serine protease inhibitors with the superbase normalized Stratum Corneum integrity/cohesion. The superbases also delayed permeability barrier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, resulting in a lipid-processing defect on electron microscopy. These studies demonstrate unequivocally that Stratum Corneum neutralization alone provokes Stratum Corneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased Stratum Corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.

  • glycerol regulates Stratum Corneum hydration in sebaceous gland deficient asebia mice
    Journal of Investigative Dermatology, 2003
    Co-Authors: Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Philip W. Wertz, Man Maoqiang, John P Sundberg, Peter M. Elias
    Abstract:

    The only known function of human sebaceous glands is the provocation of acne. We assessed here whether sebum influences Stratum Corneum hydration or permeability barrier function in asebia J1 and 2 J mice, with profound sebaceous gland hypoplasia. Asebia J1 mice showed normal permeability barrier homeostasis and extracellular lamellar membrane structures, but they displayed epidermal hyperplasia, inflammation, and decreased (>50%) Stratum Corneum hydration, associated with a reduction in sebaceous gland lipids (wax diesters/monoesters, sterol esters). The triglyceride content of both asebia and control Stratum Corneum was low, consistent with high rates of triglyceride hydrolysis within the normal pilosebaceous apparatus, despite high rates of triglyceride synthesis. Although a mixture of synthetic, sebum-like lipids (sterol/wax esters, triglycerides) did not restore normal Stratum Corneum hydration to asebia skin, topical glycerol, the putative product of triglyceride hydrolysis in sebaceous glands, normalized Stratum Corneum hydration, and the glycerol content of asebia Stratum Corneum was 85% lower than in normal Stratum Corneum. In contrast, another potent endogenous humectant (urea) did not correct the abnormality. The importance of glycerol generation from triglyceride in sebaceous glands for Stratum Corneum hydration was demonstrated further by (i) the absence of sebaceous-gland-associated lipase activity in asebia mice, whereas abundant enzyme activity was present in the glands of control mice; and (ii) the inability of high concentrations of topical triglyceride to correct the hydration abnormality, despite the presence of abundant lipase activity in asebia Stratum Corneum. These results show that sebaceous-gland-derived glycerol is a major contributor to Stratum Corneum hydration.

  • pH directly regulates epidermal permeability barrier homeostasis, and Stratum Corneum integrity/cohesion.
    The Journal of investigative dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (

  • generation of free fatty acids from phospholipids regulates Stratum Corneum acidification and integrity
    Journal of Investigative Dermatology, 2001
    Co-Authors: Joachim W Fluhr, Peter M. Elias, Kenneth R. Feingold, Mahendra Kumar Jain
    Abstract:

    There is evidence that the "acid mantle" of the Stratum Corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the Stratum Corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to Stratum Corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA 2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered Stratum Corneum integrity (number of strippings required to break the barrier) and decreased Stratum Corneum cohesion (protein weight removed per stripping). Not only Stratum Corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine Stratum Corneum to a neutral pH for as little as 3 h produced comparable abnormalities in Stratum Corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in Stratum Corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the Stratum Corneum (shown by immunofluorescence staining and vizualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal Stratum Corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of Stratum Corneum integrity and cohesion.

Kenneth R. Feingold - One of the best experts on this subject based on the ideXlab platform.

  • ph directly regulates epidermal permeability barrier homeostasis and Stratum Corneum integrity cohesion
    Journal of Investigative Dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (<20 min) of serine proteases, assessed by in situ zymography, followed by serine-protease-mediated degradation of corneodesmosomes. Western blotting revealed degradation of desmoglein 1, a key corneodesmosome structural protein, in parallel with loss of corneodesmosomes. Coapplication of serine protease inhibitors with the superbase normalized Stratum Corneum integrity/cohesion. The superbases also delayed permeability barrier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, resulting in a lipid-processing defect on electron microscopy. These studies demonstrate unequivocally that Stratum Corneum neutralization alone provokes Stratum Corneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased Stratum Corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.

  • glycerol regulates Stratum Corneum hydration in sebaceous gland deficient asebia mice
    Journal of Investigative Dermatology, 2003
    Co-Authors: Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Philip W. Wertz, Man Maoqiang, John P Sundberg, Peter M. Elias
    Abstract:

    The only known function of human sebaceous glands is the provocation of acne. We assessed here whether sebum influences Stratum Corneum hydration or permeability barrier function in asebia J1 and 2 J mice, with profound sebaceous gland hypoplasia. Asebia J1 mice showed normal permeability barrier homeostasis and extracellular lamellar membrane structures, but they displayed epidermal hyperplasia, inflammation, and decreased (>50%) Stratum Corneum hydration, associated with a reduction in sebaceous gland lipids (wax diesters/monoesters, sterol esters). The triglyceride content of both asebia and control Stratum Corneum was low, consistent with high rates of triglyceride hydrolysis within the normal pilosebaceous apparatus, despite high rates of triglyceride synthesis. Although a mixture of synthetic, sebum-like lipids (sterol/wax esters, triglycerides) did not restore normal Stratum Corneum hydration to asebia skin, topical glycerol, the putative product of triglyceride hydrolysis in sebaceous glands, normalized Stratum Corneum hydration, and the glycerol content of asebia Stratum Corneum was 85% lower than in normal Stratum Corneum. In contrast, another potent endogenous humectant (urea) did not correct the abnormality. The importance of glycerol generation from triglyceride in sebaceous glands for Stratum Corneum hydration was demonstrated further by (i) the absence of sebaceous-gland-associated lipase activity in asebia mice, whereas abundant enzyme activity was present in the glands of control mice; and (ii) the inability of high concentrations of topical triglyceride to correct the hydration abnormality, despite the presence of abundant lipase activity in asebia Stratum Corneum. These results show that sebaceous-gland-derived glycerol is a major contributor to Stratum Corneum hydration.

  • pH directly regulates epidermal permeability barrier homeostasis, and Stratum Corneum integrity/cohesion.
    The Journal of investigative dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (

  • generation of free fatty acids from phospholipids regulates Stratum Corneum acidification and integrity
    Journal of Investigative Dermatology, 2001
    Co-Authors: Joachim W Fluhr, Peter M. Elias, Kenneth R. Feingold, Mahendra Kumar Jain
    Abstract:

    There is evidence that the "acid mantle" of the Stratum Corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the Stratum Corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to Stratum Corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA 2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered Stratum Corneum integrity (number of strippings required to break the barrier) and decreased Stratum Corneum cohesion (protein weight removed per stripping). Not only Stratum Corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine Stratum Corneum to a neutral pH for as little as 3 h produced comparable abnormalities in Stratum Corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in Stratum Corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the Stratum Corneum (shown by immunofluorescence staining and vizualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal Stratum Corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of Stratum Corneum integrity and cohesion.

Jeanpierre Hachem - One of the best experts on this subject based on the ideXlab platform.

  • ph directly regulates epidermal permeability barrier homeostasis and Stratum Corneum integrity cohesion
    Journal of Investigative Dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (<20 min) of serine proteases, assessed by in situ zymography, followed by serine-protease-mediated degradation of corneodesmosomes. Western blotting revealed degradation of desmoglein 1, a key corneodesmosome structural protein, in parallel with loss of corneodesmosomes. Coapplication of serine protease inhibitors with the superbase normalized Stratum Corneum integrity/cohesion. The superbases also delayed permeability barrier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, resulting in a lipid-processing defect on electron microscopy. These studies demonstrate unequivocally that Stratum Corneum neutralization alone provokes Stratum Corneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased Stratum Corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.

  • pH directly regulates epidermal permeability barrier homeostasis, and Stratum Corneum integrity/cohesion.
    The Journal of investigative dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (

Debra Crumrine - One of the best experts on this subject based on the ideXlab platform.

  • ph directly regulates epidermal permeability barrier homeostasis and Stratum Corneum integrity cohesion
    Journal of Investigative Dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (<20 min) of serine proteases, assessed by in situ zymography, followed by serine-protease-mediated degradation of corneodesmosomes. Western blotting revealed degradation of desmoglein 1, a key corneodesmosome structural protein, in parallel with loss of corneodesmosomes. Coapplication of serine protease inhibitors with the superbase normalized Stratum Corneum integrity/cohesion. The superbases also delayed permeability barrier recovery, attributable to decreased beta-glucocerebrosidase activity, assessed zymographically, resulting in a lipid-processing defect on electron microscopy. These studies demonstrate unequivocally that Stratum Corneum neutralization alone provokes Stratum Corneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased Stratum Corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.

  • glycerol regulates Stratum Corneum hydration in sebaceous gland deficient asebia mice
    Journal of Investigative Dermatology, 2003
    Co-Authors: Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Philip W. Wertz, Man Maoqiang, John P Sundberg, Peter M. Elias
    Abstract:

    The only known function of human sebaceous glands is the provocation of acne. We assessed here whether sebum influences Stratum Corneum hydration or permeability barrier function in asebia J1 and 2 J mice, with profound sebaceous gland hypoplasia. Asebia J1 mice showed normal permeability barrier homeostasis and extracellular lamellar membrane structures, but they displayed epidermal hyperplasia, inflammation, and decreased (>50%) Stratum Corneum hydration, associated with a reduction in sebaceous gland lipids (wax diesters/monoesters, sterol esters). The triglyceride content of both asebia and control Stratum Corneum was low, consistent with high rates of triglyceride hydrolysis within the normal pilosebaceous apparatus, despite high rates of triglyceride synthesis. Although a mixture of synthetic, sebum-like lipids (sterol/wax esters, triglycerides) did not restore normal Stratum Corneum hydration to asebia skin, topical glycerol, the putative product of triglyceride hydrolysis in sebaceous glands, normalized Stratum Corneum hydration, and the glycerol content of asebia Stratum Corneum was 85% lower than in normal Stratum Corneum. In contrast, another potent endogenous humectant (urea) did not correct the abnormality. The importance of glycerol generation from triglyceride in sebaceous glands for Stratum Corneum hydration was demonstrated further by (i) the absence of sebaceous-gland-associated lipase activity in asebia mice, whereas abundant enzyme activity was present in the glands of control mice; and (ii) the inability of high concentrations of topical triglyceride to correct the hydration abnormality, despite the presence of abundant lipase activity in asebia Stratum Corneum. These results show that sebaceous-gland-derived glycerol is a major contributor to Stratum Corneum hydration.

  • pH directly regulates epidermal permeability barrier homeostasis, and Stratum Corneum integrity/cohesion.
    The Journal of investigative dermatology, 2003
    Co-Authors: Jeanpierre Hachem, Debra Crumrine, Kenneth R. Feingold, Barbara E Brown, Joachim W Fluhr, Peter M. Elias
    Abstract:

    Both exposure of Stratum Corneum to neutral pH buffers and blockade of acidification mechanisms disturb cutaneous permeability barrier homeostasis and Stratum Corneum integrity/cohesion, but these approaches all introduce potentially confounding variables. To study the consequences of Stratum Corneum neutralization, independent of hydration, we applied two chemically unrelated superbases, 1,1,3,3-tetramethylguanidine or 1,8-diazabicyclo [5,4,0] undec-7-ene, in propylene glycol:ethanol (7:3) to hairless mouse skin and assessed whether discrete pH changes alone regulate cutaneous permeability barrier function and Stratum Corneum integrity/cohesion, as well as the responsible mechanisms. Both 1,1,3,3-tetramethylguanidine and 1,8-diazabicyclo [5,4,0] undec-7-ene applications increased skin surface pH in parallel with abnormalities in both barrier homeostasis and Stratum Corneum integrity/cohesion. The latter was attributable to rapid activation (