IL‑18 knockout alleviates atopic dermatitis‑like skin lesions induced by MC903 in a mouse model

Chen,Jia‑Long; Niu,Xue‑Li; Gao,Ya‑Li; Ma,Lei; Gao,Xing‑Hua; Chen,Hong‑Duo; Qi,Rui‑Qun

doi:10.3892/ijmm.2020.4630

IL‑18 knockout alleviates atopic dermatitis‑like skin lesions induced by MC903 in a mouse model

Authors:
- Jia‑Long Chen
- Xue‑Li Niu
- Ya‑Li Gao
- Lei Ma
- Xing‑Hua Gao
- Hong‑Duo Chen
- Rui‑Qun Qi
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Affiliations: Graduate School, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Dermatology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, P.R. China
Published online on: June 4, 2020 https://doi.org/10.3892/ijmm.2020.4630
Pages: 880-888

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Abstract

Interleukin (IL)‑18, a pro‑inflammatory cytokine, plays an important role in a number of skin diseases. The aim of the present study was to investigate the role of IL‑18 in the development of atopic dermatitis (AD). For this purpose, mice were divided into 4 groups (n=5/group) as follows: i) The wild‑type (WT) controls; ii) IL18 knockout (KO) controls; iii) MC903‑treated WT mice; and iv) MC903‑treated KO mice. MC903 (4 nmol in ethanol) was topically applied daily for 15 consecutive days to the exposed skins of mice. AD‑like symptoms and severity were evaluated by the scoring of AD (SCORAD). Serum immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP) levels were determined with the use of an enzyme‑linked immunosorbent assay. Immunohistochemistry was used to assess the expression of IL‑1β, signal transducer and activator of transcription (STAT)3 and filaggrin (FLG) in the skin lesions. RT‑qPCR was performed to assess the mRNA levels of IL‑1β, IL‑4, IL‑9, STAT3, corticotropin‑releasing hormone receptor (CRHR)1, CRHR2, TSLP and caspase‑1 in the skin lesions. It was demonstrated that IL‑18 may function as a pleiotropic pro‑inflammatory cytokine in the development of AD‑like lesions. IL‑18 KO reduced aggravated AD‑like lesions induced by MC903, in part by upregulating Th2 cytokines. IL‑18 promoted the expression of FLG in the epidermis and CRHR2 in AD‑like lesions, but downregulated the serum levels of IgE. On the whole, the findings of the present study demonstrate that IL‑18 deficiency alleviates AD‑induced lesions in mice.

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