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

Karin M. Aberg, Katherine A. Radek, Eung Ho Choi, Dong Kun Kim, Marianne Demerjian, Melanie Hupe, Joseph Kerbleski, Richard L. Gallo, Tomas Ganz, Theodora Mauro, Kenneth R. Feingold, Peter M. Elias

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and β-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens.

Original languageEnglish
Pages (from-to)3339-3349
Number of pages11
JournalJournal of Clinical Investigation
Volume117
Issue number11
DOIs
Publication statusPublished - 2007 Nov 1

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Psychological Stress
Glucocorticoids
Down-Regulation
Skin
Peptides
Topical Administration
Infection
Streptococcus pyogenes
Lipids
Defensins
Corticotropin-Releasing Hormone
Epidermis
Hormones
Pharmacology

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Aberg, Karin M. ; Radek, Katherine A. ; Choi, Eung Ho ; Kim, Dong Kun ; Demerjian, Marianne ; Hupe, Melanie ; Kerbleski, Joseph ; Gallo, Richard L. ; Ganz, Tomas ; Mauro, Theodora ; Feingold, Kenneth R. ; Elias, Peter M. / Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 11. pp. 3339-3349.
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abstract = "The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and β-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens.",
author = "Aberg, {Karin M.} and Radek, {Katherine A.} and Choi, {Eung Ho} and Kim, {Dong Kun} and Marianne Demerjian and Melanie Hupe and Joseph Kerbleski and Gallo, {Richard L.} and Tomas Ganz and Theodora Mauro and Feingold, {Kenneth R.} and Elias, {Peter M.}",
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Aberg, KM, Radek, KA, Choi, EH, Kim, DK, Demerjian, M, Hupe, M, Kerbleski, J, Gallo, RL, Ganz, T, Mauro, T, Feingold, KR & Elias, PM 2007, 'Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice', Journal of Clinical Investigation, vol. 117, no. 11, pp. 3339-3349. https://doi.org/10.1172/JCI31726

Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice. / Aberg, Karin M.; Radek, Katherine A.; Choi, Eung Ho; Kim, Dong Kun; Demerjian, Marianne; Hupe, Melanie; Kerbleski, Joseph; Gallo, Richard L.; Ganz, Tomas; Mauro, Theodora; Feingold, Kenneth R.; Elias, Peter M.

In: Journal of Clinical Investigation, Vol. 117, No. 11, 01.11.2007, p. 3339-3349.

Research output: Contribution to journalArticle

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T1 - Psychological stress downregulates epidermal antimicrobial peptide expression and increases severity of cutaneous infections in mice

AU - Aberg, Karin M.

AU - Radek, Katherine A.

AU - Choi, Eung Ho

AU - Kim, Dong Kun

AU - Demerjian, Marianne

AU - Hupe, Melanie

AU - Kerbleski, Joseph

AU - Gallo, Richard L.

AU - Ganz, Tomas

AU - Mauro, Theodora

AU - Feingold, Kenneth R.

AU - Elias, Peter M.

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N2 - The skin is the first line of defense against microbial infection, and psychological stress (PS) has been shown to have adverse effects on cutaneous barrier function. Here we show that PS increased the severity of group A Streptococcus pyogenes (GAS) cutaneous skin infection in mice; this was accompanied by increased production of endogenous glucocorticoids (GCs), which inhibited epidermal lipid synthesis and decreased lamellar body (LB) secretion. LBs encapsulate antimicrobial peptides (AMPs), and PS or systemic or topical GC administration downregulated epidermal expression of murine AMPs cathelin-related AMP and β-defensin 3. Pharmacological blockade of the stress hormone corticotrophin-releasing factor or of peripheral GC action, as well as topical administration of physiologic lipids, normalized epidermal AMP levels and delivery to LBs and decreased the severity of GAS infection during PS. Our results show that PS decreases the levels of 2 key AMPs in the epidermis and their delivery into LBs and that this is attributable to increased endogenous GC production. These data suggest that GC blockade and/or topical lipid administration could normalize cutaneous antimicrobial defense during PS or GC increase. We believe this to be the first mechanistic link between PS and increased susceptibility to infection by microbial pathogens.

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