Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility
| Autor: | Ken, Natsuga, Sara, Cipolat, Fiona M, Watt |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Skin Neoplasms
Epidemiology Skin Absorption FISH fluorescence in situ hybridization MPO myeloperoxidase Enzyme-Linked Immunosorbent Assay Real-Time Polymerase Chain Reaction EPI-/- mice mice lacking envoplakin periplakin and involucrin Statistics Nonparametric SPF specific pathogen free Mice Animals Protein Precursors In Situ Hybridization Fluorescence Peroxidase Skin Analysis of Variance NKG2D natural killer group 2D integumentary system AMP antimicrobial protein Microbiota Membrane Proteins WT wild-type Bacterial Load Anti-Bacterial Agents Mice Inbred C57BL Disease Models Animal Female Original Article Disease Susceptibility TPA tetradecanoylphorbol-13-acetate Antimicrobial Cationic Peptides |
| Zdroj: | The Journal of Investigative Dermatology |
| ISSN: | 1523-1747 |
| Popis: | Mice lacking three epidermal barrier proteins-envoplakin, periplakin, and involucrin (EPI-/- mice)-have a defective cornified layer, reduced epidermal γδ T cells, and increased dermal CD4(+) T cells. They are also resistant to developing skin tumors. The tumor-protective mechanism involves signaling between Rae-1 expressing keratinocytes and the natural killer group 2D receptor on immune cells, which also plays a role in host defenses against infection. Given the emerging link between bacteria and cancer, we investigated whether EPI-/- mice have an altered skin microbiota. The bacterial phyla were similar in wild-type and EPI-/- skin. However, bacteria were threefold more abundant in EPI-/- skin and penetrated deeper into the epidermis. The major epithelial defense mechanism against bacteria is production of antimicrobial proteins (AMPs). EPI-/- skin exhibited enhanced expression of antimicrobial peptides. However, reducing the bacterial load by antibiotic treatment or breeding mice under specific pathogen-free conditions did not reduce AMP expression or alleviate the abnormalities in T-cell populations. We conclude that the atopic characteristics of EPI-/- skin are a consequence of the defective barrier rather than a response to the increased bacterial load. It is therefore unlikely that the increase in skin microbiota contributes directly to the observed cancer resistance. |
| Databáze: | OpenAIRE |
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