J Vet Sci.  2010 Sep;11(3):213-220. 10.4142/jvs.2010.11.3.213.

Inhibitory effects of interleukin-10 plasmid DNA on the development of atopic dermatitis-like skin lesions in NC/Nga mice

• Jung BG
• Cho SJ
• Ko JH
• Lee BJ

• KMID: 1093495
• DOI: http://doi.org/10.4142/jvs.2010.11.3.213

Abstract

Interleukin (IL)-10 exerts potent anti-inflammatory effects by suppression of both T-help (Th) 1 and Th2 cells. Previous studies have reported that IL-10 can ameliorate various inflammatory disorders. The present study was performed to examine whether IL-10 plasmid DNA could suppress development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice, as an initial step towards the development of an appliance for use in dogs with AD. Intradermal injection of IL-10 plasmid DNA markedly inhibited the development of AD-like skin lesions, as evidenced by a marked decrease in skin symptoms and reduced inflammation within the skin lesions. Efficacy was confirmed by significant decreases in eosinophil ratio and serum IgE concentration, and a reduction in the number of Staphylococcus aureus recovered from the ear. Moreover, relative mRNA expression levels of IL-4 and interferon-gamma in the skin lesions of mice injected with IL-10 plasmid DNA were also decreased compared with those of control mice. Of note, higher serum IL-10 levels in mice injected with IL-10 plasmid DNA were maintained compared with those in control mice. Taken together, the results indicate that IL-10 plasmid DNA can suppress the development of AD-like skin lesions by suppressing both Th1 and Th2 cell responses. Beneficial effects of IL-10 plasmid DNA may be expected in dogs with AD.

Keyword

atopic dermatitis; IL-10; NC/Nga mice; plasmid DNA

MeSH Terms

Animals
Case-Control Studies
DNA Primers/genetics
Dermatitis, Atopic/immunology/*prevention & control
Disease Models, Animal
Dogs
Female
Interleukin-10/genetics/*immunology/*therapeutic use
Mice
Mice, Mutant Strains
Plasmids/genetics/*therapeutic use
Staphylococcus aureus/isolation & purification
Statistics, Nonparametric
T-Lymphocytes, Helper-Inducer/*immunology

Figure

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  Fig. 1 Induction of dermatitis and interleukin (IL)-10 plasmid DNA injection schedule. Dorsal regions of mice were shaved on day 0. The hairless dorsal regions and glabrous ears of mice were sensitized with 200 µL of 1% (w/v) DNCB solution on day 4. Three days after sensitization, the dorsal skin and ears were challenged with 150 µL of 0.2% (w/v) DNCB solution every 3 days. Following in vivo delivery of IL-10 plasmid DNA, mice were intradermally injected with 100 µg of IL-10 plasmid DNA in 100 µL of phosphate-buffered saline (PBS) or PBS alone (control) on days 1 and 8 of experiment.

• 

  Fig. 2 Clinical skin severity score in the control mice increased gradually with the number of cutaneous applications of DNCB and reached a peak at the end of experiment. A significant improvement in mice injected with IL-10 plasmid DNA had occurred at day 13 (*p<0.05) and by day 16 was even more pronounced (**p<0.01) compared with the control mice (mean ± SD; n = 5).

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  Fig. 3 The skin features demonstrated visually a marked reduction in severity of the dermatitis and more rapid hair re-growth with IL-10 plasmid DNA injection. (A) Dermatitis induced and PBS injected mice, (B) IL-10 plasmid DNA injected mice after dermatitis induction.

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  Fig. 4 Histological features of dorsal skin and dermal mast cell infiltration. (A) Hyperplastic epidermis and inflammatory cells were notable. (B) The inflammatory infiltrate was less severe in mice injected with plasmid DNA. H&E stain, Scale bar = 100 µm. (C) More severe infiltration of mast cells was evident in control mice. (D) The mast cell infiltrate was less severe in plasmid DNA injected mice. Toluidine blue stain, Scale bar = 50 µm.

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  Fig. 5 The inhibitory effects of interleukin-10 plasmid DNA. The concentration of serum IL-10 in mice injected with IL-10 plasmid DNA was significantly higher than in control mice. *p < 0.05 vs. control, **p < 0.01 vs. control.

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