The enzymes that build the skin barrier work in an acidic environment

The lipids that make the skin waterproof are assembled in the stratum corneum by enzymes, and these enzymes have their optimal activity in an acidic environment. When the surface pH rises, research observes a barrier that is slower to rebuild and a stratum corneum that is less cohesive.

This mechanism largely explains why the skin's natural acidity is of such interest to researchers. It takes place on a scale of a few micrometres, in the most superficial layers of the epidermis.

The cement of the stratum corneum

The stratum corneum is often compared to a wall. The bricks are the corneocytes, flattened cells filled with keratin. The cement is a set of lipids arranged in fine lamellae between these cells.

This cement combines three families of lipids: ceramides, cholesterol and free fatty acids. Organised in superimposed layers, they slow down water evaporation and form the essential part of the permeability barrier.

Lipids delivered as precursors

These lipids begin their existence as precursors. The cells of the epidermis produce them and store them in small organelles called lamellar bodies. At the moment the cell transforms into a corneocyte, it releases this content into the space between the cells.

The precursors must then be transformed on site. Several enzymes take care of this:

  • β-glucocerebrosidase converts glucosylceramides into ceramides;
  • acid sphingomyelinase converts sphingomyelin into ceramides;
  • a secretory phospholipase releases fatty acids from phospholipids.

Without this step, the lamellae remain immature. Researchers blocked β-glucocerebrosidase on mouse skin. Glucosylceramides accumulated, immature membrane structures persisted between the cells and barrier function declined progressively. The effect was reversible when the inhibitor was stopped (Holleran et al., 1993).

An optimum at acidic pH

These enzymes of lipid maturation have optimal activity at acidic pH. This is particularly well documented for β-glucocerebrosidase (Mauro et al., 1998). Acid sphingomyelinase, as its name indicates, also works in an acidic environment. Its activity decreases when the stratum corneum is neutralised (Hachem et al., 2005).

The acidity of the stratum corneum thus appears as a working condition for these enzymes.

What happens when the pH rises

Experimental studies carried out on mouse skin have observed what happens to these enzymes when the pH of the stratum corneum is raised. The activity of β-glucocerebrosidase decreases and barrier repair starts more slowly at neutral or alkaline pH (Mauro et al., 1998; Hachem et al., 2003). When the elevation is prolonged, β-glucocerebrosidase and acid sphingomyelinase end up being degraded by other enzymes of the stratum corneum, the serine proteases (Hachem et al., 2005).

The consequences for the cohesion of the stratum corneum are detailed in the article “What happens at the skin surface when its pH rises”.

What this work allows us to say

These results come mainly from animal models, using chemical means intended to raise the pH strongly. They describe a mechanism. They do not measure the effect of a given shower or cleanser in a person.

They do, however, shed light on an observation made in humans. In a study of 330 volunteers, skin areas whose surface pH was below 5 showed better barrier and hydration parameters than the others (Lambers et al., 2006). The link between surface acidity and barrier quality is therefore coherent, from the enzyme to the whole skin.

A daily task

The skin barrier renews itself constantly. It is assembled every day by these enzymes, layer after layer, in the acidic environment of the stratum corneum.

On a daily basis, measured cleansing limits variations in this environment: lukewarm water, brief washing, careful rinsing.

This article is part of the PHYTO 5 Library.

Sources

  1. Hachem JP, Crumrine D, Fluhr J, Brown BE, Feingold KR, Elias PM. pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion. Journal of Investigative Dermatology. 2003;121(2):345-353. DOI : 10.1046/j.1523-1747.2003.12365.x
  2. Hachem JP, Man MQ, Crumrine D, Uchida Y, Brown BE, Rogiers V, Roseeuw D, Feingold KR, Elias PM. Sustained serine proteases activity by prolonged increase in pH leads to degradation of lipid processing enzymes and profound alterations of barrier function and stratum corneum integrity. Journal of Investigative Dermatology. 2005;125(3):510-520. DOI : 10.1111/j.0022-202X.2005.23838.x
  3. Holleran WM, Takagi Y, Menon GK, Legler G, Feingold KR, Elias PM. Processing of epidermal glucosylceramides is required for optimal mammalian cutaneous permeability barrier function. Journal of Clinical Investigation. 1993;91(4):1656-1664. DOI : 10.1172/JCI116374
  4. Lambers H, Piessens S, Bloem A, Pronk H, Finkel P. Natural skin surface pH is on average below 5, which is beneficial for its resident flora. International Journal of Cosmetic Science. 2006;28(5):359-370. DOI : 10.1111/j.1467-2494.2006.00344.x
  5. Mauro T, Holleran WM, Grayson S, Gao WN, Man MQ, Kriehuber E, Behne M, Feingold KR, Elias PM. Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing. Archives of Dermatological Research. 1998;290(4):215-222. DOI : 10.1007/s004030050293
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