Elias and Williams: The Inside-Out of Skin by dermatologists and skin researchers Peter M. Elias, M.D. and Mary L. Williams, M.D.

The Inside-Out of Skin

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Research from the Elias Lab

For nearly forty years, this University of California San Francisco-based research laboratory has focused on elucidating the structural and metabolic basis for the barrier function of the skin, including work aimed at understanding the cause and treatment of skin diseases.

Our Sour Skin Surface

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Did you know that the surface of our skin is acidic? That we have a sour skin surface, like vinegar or lemon juice?  Scientists have long known that we are covered by an acid mantle. But how the epidermis – the outer layers of skin – achieves this feat, conferring a pH of 5.0 or less to our skin surface, when the cells of our body and the blood and fluids bathing those cells have a more neutral pH of ~7.4, has until recently been something of a mystery. lemons crop2

 

To our surprise, as we were studying the characteristics of epidermis in relation to skin pigmentation, we noted that the pH of darkly pigmented stratum corneum is  lower – that is, it is more acidic – than the surface of lightly pigmented skin. We saw that the pH of darkly pigmented skin was lower by about a half a unit – from ~5.0-5.5 in lighter skin to ~5.0-4.5 in darker skin . While that may seem like a small difference, it is actually rather huge. Differences in skin pH are a bit like those in earthquakes measured on the Richter scale, because both are logarithmic scales. Thus, a change of half a pH unit denotes a 50-fold more acidic environment! [Read more…] about Our Sour Skin Surface

Highlights from the 2013 IID. Part 7: Is Acne a Disorder of the Skin Barrier?

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It has been known for decades that the formation of keratinous plugs in the outlet of the sebaceous follicles is the first step in the process of acne vulgaris.  These ‘comedones’, (called ‘open comedones’ (blackheads) if the opening of the pore is wide and the plug is visible; and ‘closed comedones’ (whiteheads) if it is tiny and the plug buried under the surface), precede the development of inflammatory lesions (what we call pimples). It has also been known for a long time that individuals who develop more than their fair share of acne have oily skin.  Or, more precisely, they tend to have high rates of sebum production.

Downing and colleagues linked these two observations together and proposed that comedones are the result of essential fatty acid deficiency in the follicular orifice.  Deficiency of the essential fatty acid, linoleic acid, produces a dermatitis characterized by scaling, redness or erythema, and a defective permeability barrier.  This is because linoleic acid is a critical constituent of some of the ceramides that are required  for the skin barrier. Sebum is rich in other fatty acids, but it lacks linoleic acid. Therefore, the epidermal cells lining the follicle, which are continually bathed in this deficient lipid mixture, could develop a form of localized essential fatty acid deficiency. The more sebum being produced, the greater this dilutional effect. Little has been done to test the Downing hypothesis since it was first espoused twenty five years ago.  A first step in that direction would be to determine whether or not there is a barrier defect in the follicular epithelium.

In the studies reported here, we examined the barrier integrity of different regions of the hair follicle in biopsies of non-inflamed, open comedones, using a water-soluble tracer that can be seen with an electron microscope. While normal follicles show an intact barrier from the skin surface all the way down to the opening of the sebaceous gland, follicle walls surrounding open comedones leaked abundant tracer.

Bottom Line: These studies indicate that an barrier defect in the hair follicle wall is present in the earliest lesions of acne.  It raises the possibility that treatments aimed at restoration of the barrier in early acne lesions might prevent the later development of inflammatory acne.

Highlights of the 2013 IID. Part 6: Does barrier repair therapy improve skin defense against infection?

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Prior work from our group has shown that the permeability and antimicrobial barriers in normal skin share many common features, and are co-regulated, such that perturbations in one function inevitably impact the other. We also showed that a variety of conditions that compromise the permeability barrier, including neonatal and aging skin, are also accompanied by a reduction in the production of the cathelicidin antimicrobial peptide, LL-37, a key defender against S. Aureus and Streptococcal infections.

In this study, we asked whether strategies that improve permeability barrier function also enhance production of LL-37. [Read more…] about Highlights of the 2013 IID. Part 6: Does barrier repair therapy improve skin defense against infection?

HIghlights of the 2013 IID. Part 4: The Good Side of Psychological Stress

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It is widely held that the stress of our modern lives is bad for our health. And it is certainly true that stress (or, more precisely, ‘psychological stress’) can be harmful to the function of our skin. It delays wound healing. It can reduce our immune defenses against infection.  And, as we demonstrated several years ago, it can compromise the skin’s permeability barrier. It is also accepted by many that stress exacerbates chronic inflammatory diseases, like rheumatic disorders and inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease, as well as skin conditions, like psoriasis and eczema (atopic dermatitis).

It makes sense, of course, that the stress response to acute threats – like a tiger attack – was beneficial to early man.  This is the famous “Fight or Flight” response system. But why has the stress response to chronic challenges, like illness, persisted? If the effects of psychological stress during illness are all bad – then would not mutations that weakened this deleterious stress response have been favored by natural selection long ago? The answer, as we reported here, may be that the stress response to illness is, in fact,  not always harmful. [Read more…] about HIghlights of the 2013 IID. Part 4: The Good Side of Psychological Stress

HIghlights of the IID. Part 3: How Melanin Is Good For The Skin Barrier

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In previous work, we demonstrated that the skin of darkly-pigmented people possesses a tighter, more competent barrier to water leakage than does the skin of lightly-pigmented individuals.  Although we could attribute this to the much more acidic (lower pH) skin surface in individuals with dark pigmentation, just how either melanin or its parent cell, the melanocyte, confers these benefits was unknown.

For the studies reported here, we took advantage of two closely related strains of hairless mice – one that is darkly pigmented (hrs/J), and a a closely-related strain that is pink or albino (hr/hr). As expected, the barrier was better in the pigmented mice, and these darker mice, like their more heavily pigmented human counterparts, also exhibited a more acidic stratum corneum. In the pigmented mice (just as in darkly pigmented human skin), melanin granules persisted out into the stratum corneum, and eventually some of these granules are released into the spaces between the cells of the stratum corneum (corneocytes).  [Read more…] about HIghlights of the IID. Part 3: How Melanin Is Good For The Skin Barrier