[Anti-inflammatory effect of interleukin-35 in mice with colitis and its mechanism]
Zhanjun Lu1,2,3, Yangyang Hu2,3, Sisi Li2,3
1Department of Gastroenterology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China.
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 P<0.01). Compared with the control group, the colon length was significantly shortened in the model group (P<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 (P>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 P<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 P<0.05). Compared with the control group, the proportion of M1 macrophages in the model group increased (P<0.05), while the proportion of M1 macrophages in the IL-35-treated group was lower than that in the model group (P<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 P<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.
Insights
Interleukin-35 (IL-35) demonstrates anti-inflammatory effects in colitis models by reducing pro-inflammatory cytokines and M1 macrophage polarization. This study highlights IL-35
Area of Science:
- Immunology
- Gastroenterology
- Molecular Biology
Background:
- Inflammatory bowel disease (IBD) is a chronic condition characterized by inflammation of the digestive tract.
- Interleukin-35 (IL-35) is an immunosuppressive cytokine with potential therapeutic roles in inflammatory diseases.
- Understanding the mechanisms of IL-35 in IBD is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the anti-inflammatory effects of Interleukin-35 (IL-35) in a mouse model of inflammatory bowel disease (IBD).
- To elucidate the underlying mechanisms, including the modulation of macrophage polarization and cytokine expression, by which IL-35 exerts its effects in colitis.
Main Methods:
- Induction of colitis in BALB/c mice using oral administration of glucan sodium sulfate.
- Treatment with intraperitoneal injections of IL-35 in the experimental group.
- Assessment of disease activity index (DAI), colon morphology, inflammatory cell infiltration, cytokine mRNA levels (IL-6, TNF-α, IFN-γ, IL-10), macrophage polarization (M1), and SHIP1 expression (mRNA and protein).
Main Results:
- IL-35 treatment significantly reduced DAI scores and microscopic inflammatory scores in the colon compared to the model group.
- IL-35 administration led to decreased expression of pro-inflammatory cytokines (IL-6, TNF-α, IFN-γ) and increased IL-10 mRNA levels.
- IL-35 inhibited M1 macrophage polarization and increased the expression of SHIP1 in the colonic tissue.
Conclusions:
- Interleukin-35 (IL-35) exhibits significant anti-inflammatory properties in experimental colitis.
- IL-35 ameliorates colitis by suppressing M1 macrophage polarization and modulating the expression of key inflammatory cytokines.
- The findings suggest IL-35 as a potential therapeutic agent for inflammatory bowel disease.
Related Concept Videos
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:17Radical Anti-Markovnikov Addition to Alkenes: Mechanism
The mechanism starts with chain initiation, which involves two steps. In the first chain initiation step, a weak peroxide bond is homolytically cleaved upon mild heating to form two alkoxy radicals. In the second initiation step, a hydrogen atom is abstracted by the alkoxy...
01:28Inflammatory Response
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
01:24Inflammatory Response II: Inflammatory Exudate and Tissue Repair
The typical wound exudate is odorless, transparent, straw-colored, thin, and watery. Exudate, however, can differ depending on the state of wound healing. Likewise, the...
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:30Inflammatory Response I: Vascular and Cellular