Co-regulation and interdependence of the mammalian epidermal permeability and antimicrobial barriers

Karin M. Aberg, Mao Qiang Man, Richard L. Gallo, Tomas Ganz, Debra Crumrine, Barbara E. Brown, Eung Ho Choi, Dong Kun Kim, Jens M. Schröder, Kenneth R. Feingold, Peter M. Elias

Research output: Contribution to journalArticlepeer-review

179 Citations (Scopus)

Abstract

Human epidermis elaborates two small cationic, highly hydrophobic antimicrobial peptides (AMP), β-defensin 2 (hBD2), and the carboxypeptide cleavage product of human cathelicidin (hCAP18), LL-37, which are co-packaged along with lipids within epidermal lamellar bodies (LBs) before their secretion. Because of their colocalization, we hypothesized that AMP and barrier lipid production could be coregulated by altered permeability barrier requirements. mRNA and immunostainable protein levels for mBD3 and cathelin-related antimicrobial peptide (CRAMP) (murine homologues of hBD2 and LL-37, respectively) increase 1-8 hours after acute permeability barrier disruption and normalize by 24 hours, kinetics that mirror the lipid metabolic response to permeability barrier disruption. Artificial permeability barrier restoration, which inhibits the lipid-synthetic response leading to barrier recovery, blocks the increase in AMP mRNA/protein expression, further evidence that AMP expression is linked to permeability barrier function. Conversely, LB-derived AMPs are also important for permeability barrier homeostasis. Despite an apparent increase in mBD3 protein, CRAMP-/- mice delayed permeability barrier recovery, attributable to defective LB contents and abnormalities in the structure of the lamellar membranes that regulate permeability barrier function. These studies demonstrate that (1) the permeability and antimicrobial barriers are coordinately regulated by permeability barrier requirements and (2) CRAMP is required for permeability barrier homeostasis.

Original languageEnglish
Pages (from-to)917-925
Number of pages9
JournalJournal of Investigative Dermatology
Volume128
Issue number4
DOIs
Publication statusPublished - 2008 Apr

Bibliographical note

Funding Information:
These studies were supported by NIH Grants AR19098, AR39448(PP), AI059311, and the Medical Research Service, Department of Veterans Affairs, and a NIH post-doctoral fellowship (AR07175-28) to Dr Aberg. We gratefully acknowledge the excellent editorial assistance of Ms Joan Wakefield and Jerelyn Magnusson.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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