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Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility.

Natsuga K, Cipolat S, Watt FM - J. Invest. Dermatol. (2016)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom; Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

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Microbiota independent inflammatory and stress response phenotypes of EPI-/- skin. (a) qPCR of 16s RNA gene in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- ear skin samples. (b) Number of CD4+CD3+ cells per mm2 dermis. (c) Number of γδTCR+ cells per mm epidermis. (d) Number of Vγ3+ cells per mm epidermis. (e) qRT-PCR of Rae-1 in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- epidermis. (f) Quantification of MPO in WT, EPI-/-, and flora-deficient skin lysates. Data are means ± SEM from at least four (a) or three (b–f) mice per group. *P < 0.05, ****P < 0.001; unless indicated no significant differences were found (one-way ANOVA followed by Tukey’s test).
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fig3: Microbiota independent inflammatory and stress response phenotypes of EPI-/- skin. (a) qPCR of 16s RNA gene in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- ear skin samples. (b) Number of CD4+CD3+ cells per mm2 dermis. (c) Number of γδTCR+ cells per mm epidermis. (d) Number of Vγ3+ cells per mm epidermis. (e) qRT-PCR of Rae-1 in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- epidermis. (f) Quantification of MPO in WT, EPI-/-, and flora-deficient skin lysates. Data are means ± SEM from at least four (a) or three (b–f) mice per group. *P < 0.05, ****P < 0.001; unless indicated no significant differences were found (one-way ANOVA followed by Tukey’s test).

Mentions: To determine whether the increased bacterial load influenced the atopic phenotype of EPI-/- mice, we used two strategies to reduce the bacterial content of the skin. One was to breed EPI-/- mice for multiple generations under specific-pathogen-free (SPF) barrier conditions (flora-deficient EPI-/- mice). The other was to treat them systemically for 2 weeks with the broad-spectrum antibiotic enrofloxacin, a time frame chosen on the basis that the exaggerated atopic response to TPA we described previously (Cipolat et al., 2014) is induced within 9 days. Both treatments reduced the bacterial load of EPI-/- skin to that of WT control mice (Figure 3a).


Increased Bacterial Load and Expression of Antimicrobial Peptides in Skin of Barrier-Deficient Mice with Reduced Cancer Susceptibility.

Natsuga K, Cipolat S, Watt FM - J. Invest. Dermatol. (2016)

Microbiota independent inflammatory and stress response phenotypes of EPI-/- skin. (a) qPCR of 16s RNA gene in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- ear skin samples. (b) Number of CD4+CD3+ cells per mm2 dermis. (c) Number of γδTCR+ cells per mm epidermis. (d) Number of Vγ3+ cells per mm epidermis. (e) qRT-PCR of Rae-1 in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- epidermis. (f) Quantification of MPO in WT, EPI-/-, and flora-deficient skin lysates. Data are means ± SEM from at least four (a) or three (b–f) mice per group. *P < 0.05, ****P < 0.001; unless indicated no significant differences were found (one-way ANOVA followed by Tukey’s test).
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fig3: Microbiota independent inflammatory and stress response phenotypes of EPI-/- skin. (a) qPCR of 16s RNA gene in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- ear skin samples. (b) Number of CD4+CD3+ cells per mm2 dermis. (c) Number of γδTCR+ cells per mm epidermis. (d) Number of Vγ3+ cells per mm epidermis. (e) qRT-PCR of Rae-1 in WT, EPI-/-, antibiotic-treated EPI-/-, and flora-deficient EPI-/- epidermis. (f) Quantification of MPO in WT, EPI-/-, and flora-deficient skin lysates. Data are means ± SEM from at least four (a) or three (b–f) mice per group. *P < 0.05, ****P < 0.001; unless indicated no significant differences were found (one-way ANOVA followed by Tukey’s test).
Mentions: To determine whether the increased bacterial load influenced the atopic phenotype of EPI-/- mice, we used two strategies to reduce the bacterial content of the skin. One was to breed EPI-/- mice for multiple generations under specific-pathogen-free (SPF) barrier conditions (flora-deficient EPI-/- mice). The other was to treat them systemically for 2 weeks with the broad-spectrum antibiotic enrofloxacin, a time frame chosen on the basis that the exaggerated atopic response to TPA we described previously (Cipolat et al., 2014) is induced within 9 days. Both treatments reduced the bacterial load of EPI-/- skin to that of WT control mice (Figure 3a).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, United Kingdom; Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Show MeSH
Related in: MedlinePlus