Interleukin-18 exacerbates skin inflammation and affects microabscesses and scale formation in a mouse model of imiquimod-induced psoriasis.
10.1097/CM9.0000000000000140
- Author:
Xue-Li NIU
1
;
Yu HUANG
1
;
Ya-Li GAO
1
;
Yu-Zhe SUN
1
;
Yang HAN
2
;
Hong-Duo CHEN
1
;
Xing-Hua GAO
1
;
Rui-Qun QI
1
Author Information
1. Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
2. Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110001, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Chemokine CXCL1;
metabolism;
Cytokines;
metabolism;
Disease Models, Animal;
Imiquimod;
toxicity;
Interleukin-17;
metabolism;
Interleukin-18;
metabolism;
Mice;
Mice, Knockout;
Psoriasis;
chemically induced;
genetics;
metabolism;
Skin;
immunology;
metabolism
- From:
Chinese Medical Journal
2019;132(6):690-698
- CountryChina
- Language:English
-
Abstract:
BACKGROUND:As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis.
METHODS:WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC).
RESULTS:Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased.
CONCLUSIONS:IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.
