Email Alert | RSS

Journal of Peking University (Health Sciences) ›› 2024, Vol. 56 ›› Issue (5): 756-762. doi: 10.19723/j.issn.1671-167X.2024.05.002

Previous Articles     Next Articles

The role and its regulatory significance of interleukin-25 in ovalbumin induced atopic dermatitis of mice

Jiang JIN*(), Xue CHEN, Yan ZHAO, Jun JIA, Jianzhong ZHANG   

  1. Department of Dermatology, Peking University People's Hospital, Beijing 100044, China
  • Received:2021-07-27 Online:2024-10-18 Published:2024-10-16
  • Contact: Jiang JIN E-mail:PUPH_JiangJin@163.com
  • Supported by:
    the National Natural Science Foundation of China(81502720)

RICH HTML

   

PDF (PC)

Abstract:

Objective: To investigate the effect of interleukin-25 (IL-25) on ovalbumin (OVA) induced atopic dermatitis of mice, and the significance of regulating IL-25. Methods: In this study, 90 healthy male 6-week-old specific pathogen free (SPF) BALB/c mice were divided into 6 groups (15 in each group): ① subcutaneous injection of phosphate buffered saline (PBS) group (normal control group); ② subcutaneous injection of mouse IL-25 group (IL-25 group); ③ subcutaneous injection of anti-mouse IL-25 monoclonal antibody (anti-IL-25 group), each group received subcutaneous injection once a day for 1 week, 2 weeks apart, repeated daily subcutaneous injections for 1 week, 2 weeks apart, and repeated daily subcutaneous injections for 1 week, for a total of 7 weeks; ④ OVA treated group (model group); ⑤ OVA treated and IL-25 subcutaneous injection group (IL-25 treated dermatitis group); ⑥ OVA treated and anti-mouse IL-25 monoclonal antibody injection group (anti-IL-25 treated dermatitis group). The ⑤ and ⑥ groups in the process of treatment with OVA, IL-25 or anti-IL-25 antibody were given in the same way as the ② and ③ groups. Scratching behavior and skin performance of the mice were recorded during the seven-week-treatment. Twenty four hours after the final treatment, blood was taken from the mouse heart, and the serum was separated to detect the total IgE, IL-4, IL-5, IL-13, etc. The skin samples of the treatment sites were used for hematoxylin-eosin (HE) staining, immunohistochemistry, real-time PCR and Western blot detections. A single factor (ANOVA) analysis of variance was used to compare the differences in various indicators between the groups. Results: The frequency of scratches in the IL-25 treated dermatitis group was higher than that in the model group, and the scratching behavior of the anti-IL-25 treated dermatitis group was significantly lower than that in the model group. The appearance of atopic dermatitis, thickening of the epidermis and the degree of dermal inflammation in the IL-25 treated dermatitis group were more serious than those in the model group and the anti-IL-25 treated dermatitis group. The levels of serum IgE, IL-4, IL-5, and IL-13 in the IL-25 treated dermatitis group were significantly higher than that in the model group and the anti-IL-25 treated dermatitis group. There were significantly more CD4+ T cells in the dermis of IL-25 treated dermatitis group than that in the anti-IL-25 treated dermatitis group. The expression levels of filaggrin and defensin β2 proteins in the IL-25 treated dermatitis group were significantly lower than those in the model group and the anti-IL-25 treated dermatitis group. Conclusion: In the OVA induced atopic dermatitis mice model, IL-25 can significantly promote the damage of the epidermal barrier function and aggravate the OVA-induced dermatitis. Antagonizing IL-25 can alleviate OVA induced dermatitis to a certain extent.

Key words: Atopic dermatitis, Interleukin-25, Ovalbumin, Animal disease models

CLC Number: 

  • R758.2

Figure 1

Scratching times of mice in the different groups *** P < 0.001. IL-25, interleukin-25; OVA, ovalbumin. Normal, normal control group; IL-25, IL-25 group; Anti-IL-25, anti-IL-25 group; OVA, model group; OVA (IL-25), IL-25 treated dermatitis group; OVA (anti-IL-25), anti-IL-25 treated dermatitis group."

Figure 2

Histopathological findings of mice skin (HE staining) Annotations as in Figure 1. HE, hematoxylin-eosin."

Table 1

Primer sequences of IL-25 and GAPDH"

Gene Primer Sequence
IL-25Forward 5′-CAGCAAAGAGCAAGAACC-3′
Reverse 5′-CCCTGTCCAACTCATAGC-3′
GAPDHForward5′-AACAGGCGTCCCTTTCCGA-3′
Reverse 5′-GCCCAAGATGCCCTTCAGT-3′

Figure 3

Expression of IL-25 mRNA in mice skin ***P<0.001, n=15. Annotations as in Figure 1."

Table 2

Contents of serum IgE, IL-4, IL-5, and IL-13 in different mice groups (n=15, $\bar x \pm s$)"

Items Normal IL-25 Anti-IL-25 OVA OVA (IL-25) OVA (anti-IL-25)
IgE/(μg/L) 27.9±3.5 37.9±2.6aa 28.2±2.5 42.6±6.2c 66.3±8.3d 39.0±6.0b
IL-4/(ng/L) 26.2±3.6 37.0±11.1 27.9±6.3 47.1±7.7c 68.1±8.5d 42.8±15.9bb
IL-5/(ng/L) 314.6±58.1 633.9±81.1aa 325.7±72.9 784.2±86.7cc 959.8±90.2dd 696.7±84.3
IL-13/(ng/L) 334.2±29.7 424.9±66.9 349.0±48.0 507.0±24.9cc 588.4±12.7dd 473.7±24.7bb

Figure 4

Infiltration of CD4+ and CD8+ T cells in skin of the different mice groups * P < 0.05. Annotations as in Figure 1."

Figure 5

Expression of defensin β2 and filaggrin protein in skin of the different mice groups A, expression of defensin β2 protein in the skin of mice by immunohistochemistry; B, expression of filaggrin protein in the skin of mice by immunohistochemistry; C, expression of defensin β2 and filaggrin protein in the skin of mice by Western blot. * P < 0.05, n=15. Annotations as in Figure 1."

1 Barbarot S , Auziere S , Gadkari A , et al. Epidemiology of atopic dermatitis in adults: Results from an international survey[J]. Allergy, 2018, 73 (6): 1284- 1293.
doi: 10.1111/all.13401
2 Aktar MK , Kido-Nakahara M , Furue M , et al. Mutual upregulation of endothelin-1 and IL-25 in atopic dermatitis[J]. Allergy, 2015, 70 (7): 846- 854.
doi: 10.1111/all.12633
3 Fort MM , Cheung J , Yen D , et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo[J]. Immunity, 2001, 15 (6): 985- 995.
doi: 10.1016/S1074-7613(01)00243-6
4 Suto H , Nambu A , Morita H , et al. IL-25 enhances TH17 cell-mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells[J]. J Allergy Clin Immunol, 2018, 142 (5): 1500- 1509.e10.
doi: 10.1016/j.jaci.2017.12.1007
5 Senra L , Mylonas A , Kavanagh RD , et al. IL-17E (IL-25) enhances innate immune responses during skin inflammation[J]. J Invest Dermatol, 2019, 139 (8): 1732- 1742.e17.
doi: 10.1016/j.jid.2019.01.021
6 Tong X , Li B . A role of IL-25, a sibling of IL-17, in triggering psoriatic skin inflammation[J]. Sci China Life Sci, 2018, 61 (11): 1437- 1438.
doi: 10.1007/s11427-018-9330-x
7 Hagner SL , Harb H , Zhao M , et al. Farm-derived Gram-positive bacterium Staphylococcus sciuri W620 prevents asthma phenotype in HDM- and OVA-exposed mice[J]. Allergy, 2013, 68 (3): 322- 329.
doi: 10.1111/all.12094
8 Orciani M , Campanati A , Caffarini M , et al. T helper (Th)1, Th17 and Th2 imbalance in mesenchymal stem cells of adult patients with atopic dermatitis: At the origin of the problem[J]. Br J Dermatol, 2017, 176 (6): 1569- 1576.
doi: 10.1111/bjd.15078
9 Mashiko S , Mehta H , Bissonnette R , et al. Increased frequencies of basophils, type 2 innate lymphoid cells and Th2 cells in skin of patients with atopic dermatitis but not psoriasis[J]. J Dermatol Sci, 2017, 88 (2): 167- 174.
doi: 10.1016/j.jdermsci.2017.07.003
10 Furue M , Chiba T , Tsuji G , et al. Atopic dermatitis: Immune deviation, barrier dysfunction, IgE autoreactivity and new therapies[J]. Allergol Int, 2017, 66 (3): 398- 403.
doi: 10.1016/j.alit.2016.12.002
11 Kumar A , Rani L , Mhaske ST , et al. IL-3 receptor expression on activated human Th cells is regulated by IL-4, and IL-3 synergizes with IL-4 to enhance Th2 cell differentiation[J]. J Immunol, 2020, 204 (4): 819- 831.
doi: 10.4049/jimmunol.1801629
12 Ochiai S , Jagot F , Kyle RL , et al. Thymic stromal lymphopoietin drives the development of IL-13+ Th2 cells[J]. Proc Natl Acad Sci USA, 2018, 115 (5): 1033- 1038.
doi: 10.1073/pnas.1714348115
13 Coomes SM , Kannan Y , Pelly VS , et al. CD4+ Th2 cells are directly regulated by IL-10 during allergic airway inflammation[J]. Mucosal Immunol, 2017, 10 (1): 150- 161.
doi: 10.1038/mi.2016.47
14 Prout MS , Kyle RL , Ronchese F , et al. IL-4 is a key requirement for IL-4- and IL-4/IL-13-expressing CD4 Th2 subsets in lung and skin[J]. Front Immunol, 2018, 9, 1211.
doi: 10.3389/fimmu.2018.01211
15 Hönzke S , Wallmeyer L , Ostrowski A , et al. Influence of Th2 cytokines on the cornified envelope, tight junction proteins, and β-defensins in filaggrin-deficient skin equivalents[J]. J Invest Dermatol, 2016, 136 (3): 631- 639.
doi: 10.1016/j.jid.2015.11.007
16 Drislane C , Irvine AD . The role of filaggrin in atopic dermatitis and allergic disease[J]. Ann Allergy Asthma Immunol, 2020, 124 (1): 36- 43.
doi: 10.1016/j.anai.2019.10.008
17 Wallmeyer L , Dietert K , Sochorová M , et al. TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents[J]. Sci Rep, 2017, 7 (1): 774.
doi: 10.1038/s41598-017-00670-2
18 Christian L , Gerardus B , Marie-Anne V , et al. Novel microperfusion method confirms higher IL-17A and β-defensin-2 levels in psoriasis lesional skin compared to non-lesional skin[J]. J Dermatol Sci, 2016, 84 (1): 32- 33.
[1] Shan-shan BAI,Si-yi MO,Xiao-xiang XU,Yun LIU,Qiu-fei XIE,Ye CAO. Characteristics of orofacial operant test for orofacial pain sensitivity caused by occlusal interference in rats [J]. Journal of Peking University(Health Sciences), 2020, 52(1): 51-57.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright © Journal of Peking University (Health Sciences), All Rights Reserved.
Powered by Beijing Magtech Co. Ltd