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Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice.

Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice Aberg K, Radek KA, Choi EH, Kim DK, Demerjian M, Hipe M, Kerblewski J, Gallo RL, Ganz T, Mauro T, Feingold KR and Elias PM J Clin Invest, 2007, 117, 3339-3349

This recent publication by Aberg et al. examines the effect of psychological stress on skin and its barrier properties. One of the most important functions of skin is to act as a barrier, keeping our bodies protected from harmful environmental factors. Once the skin becomes dry, it can become itchy, flaky, and dry, and bacteria begin to flourish, which exacerbates the condition of dry skin. In extreme cases, dry skin can lead to dermatitis. Barrier lipids in skin are synthesised in lamellar bodies during keratinocyte differentiation. The contents of the lamellar bodies are excreted into the exterior to make up the lipid between the keratinocytes of the stratum corneum. A key function of the skin is to withstand microbial infection by containing a defence system of antimicrobial proteins (AMP). The peptides are encapsulated in the lamellar bodies and are secreted along with the lipids.

Stress can adversely impact gastrointestinal integrity, coronary artery disease, wound healing and susceptibility to infection. The mechanisms for this are unknown. This research shows that mice subjected to psychological stress (crowding, sustained lack of sleep and noise) suffered deterioration in cutaneous barrier function and an increase in severity of group A Streptococcus pyogenes infection. This was accompanied by an increased production of endogenous glucocorticoids that inhibited epidermal lipid biosynthesis and decreased lamellar body secretion. In non-stressed control mice, immunostainable AMP cathelin-related AMP (CRAMP) and [beta]-defensin 3 (the closest murine homologue of human [beta]-defensin 2) were detected in the stratum corneum. In mice under stress, there was a reduced expression of these key antimicrobial peptides, which are end products of lamellar body secretion. A decline in staining for these proteins was similarly noted in the pilosebaceous epithelia.

Additional data showed that, in fact, both systemic and topical glucocorticoid administration downregulated epidermal expression of AMP cathelin-related AMP (CRAMP) and [beta]-defensin 3 and as a result the skin became more prone to infection. Topical supplementation of specific lipid blends helped to normalise epidermal AMP levels by regulating and increasing expression of [beta]-defensin 3. There was no effect on CRAMP. Overall, though, a decreased severity of S. pyogenes infections during conditions of psychological stress was noted. A 1:1:1 blend of cholesterol, ceramides and free fatty acids was used.

Therefore, physiological lipids normalised epidermal AMP levels and delivery to lamellar bodies. Additionally, these data suggest that blocking glucocorticoids under situations of extreme stress may be beneficial to the skin and normalise the antimicrobial defence system. The work also showed that stress downregulated AMPs in pilosebaceous units consistent with the observation that acne is induced or worsened on stressful situations. If operative in other epithelia, these mechanisms could explain the increased susceptibility to infection during times of increased stress, and in skin, explain perturbed barrier function, increased epidermal permeability and delayed or prolonged cutaneous wound healing.
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Author:Knaggs, H.E.
Publication:Clinical Dermatology
Date:Mar 1, 2008
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