Anti-inflammatory effect of interleukin-35 in mice with colitis and its mechanism.
- Author:
Zhanjun LU
1
;
Yangyang HU
2
;
Sisi LI
2
;
Lijuan ZANG
3
;
Weiliang JIANG
2
;
Jianjiong WU
2
;
Xiening WU
2
;
Yue ZENG
2
;
Xingpeng WANG
1
Author Information
1. Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China.
2. Department of Gastroenterology, Shanghai General Hospital, Shanghai 200080, China.
3. Pathology Center, Shanghai General Hospital, Shanghai 200080, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Anti-Inflammatory Agents;
pharmacology;
Colitis;
drug therapy;
physiopathology;
Colon;
drug effects;
Cytokines;
genetics;
Disease Models, Animal;
Gene Expression Regulation;
drug effects;
Glucans;
pharmacology;
Interleukin-6;
genetics;
Interleukins;
pharmacology;
Macrophages;
drug effects;
Mice;
Mice, Inbred BALB C;
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases;
genetics
- From:
Journal of Zhejiang University. Medical sciences
2018;47(5):499-506
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the anti-inflammatory effect and mechanisms of interleukin-35 (IL-35) in inflammatory bowel disease.
METHODS:BALB/c mice were divided into three groups with 10 mice in each group:control group, model group (oral administration of 4% glucan sodium sulfate for 7 d) and IL-35-treated group (oral administration of 4% glucan sodium sulfate for 7 d, intraperitoneal injection of 2 μg IL-35 at d2-5). Disease activity index (DAI) was scored every day. After 7 d, the mice were sacrificed, and the serum and intestinal tissue samples were collected. The gross morphology of the colon was observed; HE staining was used to observe the pathological changes of colon tissue; flow cytometry was employed to detect the change of macrophage polarization ratio in colon tissue; the mRNA expression levels of cytokines IL-6, TNF-α, IFN-γ, IL-10 and SHIP1 in colon tissue were determined by real-time quantitative RT-PCR; the expression and distribution of SHIP1 in colon tissue was measured by immunohistochemistry; Western blotting was adopted to detect the expression level of SHIP1 protein in colonic intestinal tissues of each group.
RESULTS:The DAI scores of the mice in the model group were higher than those in the control group, while the DAI scores in the IL-35-treated group were lower than those in the model group (all <0.01). Compared with the control group, the colon length was significantly shortened in the model group (<0.05), while the colon length of the IL-35-treated group had an increasing trend compared with the model group, but the difference was not statistically significant (>0.05). Compared with the model group, microscopic inflammatory infiltration score was decreased and microscopic crypt destruction and score was significantly lower in IL-35-treated group (all <0.05). The relative expression of proinflammatory cytokines IL-6, TNF-α and IFN-γ in the colon tissue of IL-35-treated group was decreased compared with the model group, while the relative expression of IL-10 mRNA was higher than that of the model group (all <0.05). Compared with the control group, the proportion of M1 macrophages in the model group increased (<0.05), while the proportion of M1 macrophages in the IL-35-treated group was lower than that in the model group (<0.05). The relative expression of SHIP1 mRNA and protein in the colon tissue of IL-35-treated group was higher than that in the model group (all <0.05).
CONCLUSIONS:IL-35 can inhibit the polarization of M1 macrophages and regulate inflammatory cytokines to promote anti-inflammatory effect on mice with colitis.
