Comparison of the presentation of atopic dermatitis induced by trinitrochlorobenzene and house dust mite in NC/Nga mice (1)
Atopic dermatitis (AD) animal models can be categorized into 3 groups: 1) models induced by sensitizers; 2) transgenic mice which over-express or lack the expression of molecules; 3) mice that spontaneously develop AD-like skin lesions. Nishiki-nezumi Cinnamon/Nagoya (Nc/Nga) mice are included in the latter group of mice that spontaneously develop AD-like skin lesions. Nc/Nga mice are members of a mutation strain developed at Nagoya University in Japan in 1997 and are the first AD mouse model to be reported. TNCB is a hapten that is commonly used to induce AD and has been thought to evoke a primarily Th1-dominated response.
For the HDM-treated group, the hair on the back of the NC/Nga mice was shaved using an electric shaver, followed by treatment with 100 μL of 4% (w/v) sodium dodecyl sulfate to disrupt the skin barrier. After drying with 4% SDS, 100 mg/mouse of HDM allergen was applied to the prepared skin area, with the HDM application repeated twice per week for 4 weeks.
The serum IgE concentrations among the groups were significantly different.
The plots illustrate changes in signal intensities between the control group and the TNCB 2 weeks-treated group, between the control group and the TNCB 8 weeks-treated group, and between the control group and the HDM-treated group, with red and green lines indicating 2-fold up- or down-regulated intensities, respectively.
Between the control and HDM-treated groups, there were 5 significantly up-regulated and 3 significantly downregulated proteins.
The top 10 enriched GO_BP terms were immune response for the HDM-treated group, positive regulation of tyrosine phosphorylation of STAT4 protein, positive regulation of mononuclear cell proliferation, positive regulation of NK T cell activation, positive regulation of natural killer cell-mediated cytotoxicity directed against tumor cell target, response to UV-B, positive regulation of lymphocyte proliferation, positive regulation of the smooth muscle cell apoptotic process, positive regulation of natural killer cell activation, and negative regulation of interleukin (IL)-17 production. Among the KEGG results, there were 15 pathways that were significantly enriched in the HDM-treated group. Among them, cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, African trypanosomiasis, allograft rejection, and legionellosis were the top 5 enriched KEGG categories.
Clinical symptoms including erythema/hemorrhage, scarring/dryness, edema, and excoriation/erosion were most serious in the TNCB 2 weeks-treated group. The scoring of skin lesions among the groups showed significant differences. The scratching frequencies of the groups were significantly different. Compared to the control group tissue, epidermal and dermal hyperplasia, excessive keratinization, and infiltration of lymphocytes were exhibited. The TB staining results showed that the number of mast cells in the dermis was higher in the TCNB 8 weeks-treated and HDM-treated groups.
The possibility that repeated application of haptens, such as TNCB or oxazolone, over an extended period can cause skin inflammation to shift from a typical Th1-dominated delayed-type hypersensitivity response to a chronic Th2-dominated inflammatory response has been suggested. IL-9 is a pleiotropic cytokine (cell signaling molecule) produced by various cells, including mast, NK T, Th2, Th9, Th17, and regulatory T cells. The proliferation of Th9 cells and the expression of IL-9 in allergic respiratory diseases, asthma, and rhinitis. TNCB treatment over an extended period can cause skin inflammation to shift from a typical Th1-dominated delayed-type hypersensitivity response to a chronic Th2-dominated inflammatory response.