Clophosome alleviate dextran sulphate sodium‐induced colitis by regulating gut immune responses and maintaining intestinal integrity in mice

Abstract

Inflammatory bowel disease (IBD) is a chronic progressive disorder characterized by complicated gastrointestinal inflammation. Research on therapeutic agents is still urgent due to the lack of satisfactory treatments. Gut macrophages are considered to be predominant in excessive inflammatory responses. Thus, we aimed to investigate whether depletion of macrophages would have a beneficial effect on IBD and could be a potential therapeutic strategy. In this study, we established a 12‐day Dextran sodium sulphate (DSS)‐induced colitis mouse model and determined the effect of the macrophage depletion agent Clophosome (neutral clodronate liposomes; CNC). The results showed that CNC significantly alleviated the symptoms of colitis, as demonstrated by greater weight gain, decreased disease activity index (DAI) scores, and lower histopathological damage scores, as well was reduced levels of the proinflammatory cytokines interleukin (IL)‐6 and tumour necrosis factor (TNF)‐α. To investigate T cell subsets, cells were isolated from the lamina propria and cultured to analyse the expression of IL‐17A, interferon (IFN)‐γ and Foxp3 in CD4+ cells by flow cytometry. The data showed that during the process of colitis, the frequencies of CD4+IL‐17A+ T cells were significantly increased. Notably, CNC treatment markedly reduced the population of CD4+IL‐17A+ T cells, especially CD4+IL‐17A+IFN‐γ+ T cells. Furthermore, intestinal barrier integrity, as assessed by immunostaining of mucin and tight junction proteins, was severely disrupted in colitis. CNC improved the intestinal barrier by enhancing the expression of muc‐2 and occludin. In summary, our findings demonstrated that CNC successfully ameliorated DSS‐induced colitis and that its effect may be associated with inhibiting inflammatory responses and maintaining intestinal integrity.

Colon-Accumulated Gold Nanoclusters Alleviate Intestinal Inflammation and Prevent Secondary Colorectal Carcinogenesis via Nrf2-Dependent Macrophage Reprogramming

“…Meanwhile, Au distribution in other organs and serum was similar between normal and IBD mice (Figure C–H). This phenomenon may due to the destruction of colonic epithelial integrity, as well as the increase in the number and activity of phagocytic immune cells during IBD. , Taken together, GA showed specific preference for colon distribution during IBD, supporting the possible role of GA against IBD.…”

3,4-Methylenedioxy-β-Nitrostyrene Alleviates Dextran Sulfate Sodium–Induced Mouse Colitis by Inhibiting the NLRP3 Inflammasome

“…Previous studies have shown that IL-1β and IL-12 can promote the differentiation of helper T cells ( Mahida, 2000 ; Wang et al, 2021 ), and T helper 17 (Th17) cells are required for the development of IBD ( Geremia et al, 2014 ; Harbour et al, 2015 ; Alexander et al, 2022 ). IFN-γ–deficient Th17 cells maintained their Th17 phenotype but failed to induce colitis in mouse models, and IL-17A + IFN-γ + CD4 + T cells were considered to be more pathogenic ( Harbour et al, 2015 ; Tian et al, 2021 ). During DSS-induced colitis, IL-17A + IFN-γ + CD4 + T cell levels were significantly reduced after MNS treatment.…”

Signaling pathways regulating the immune function of cochlear supporting cells and their involvement in cochlear pathophysiology

“…In a zebrafish model of inflammation induced by tail amputation, beclomethasone decreases the number of macrophages that differentiate into M1 but does not affect the chemotactic migration of macrophages, strongly suggesting that the differentiation and migration of macrophages are independently regulated (Xie et al, 2019). Clophosome (clodronate disodium salt) depletes macrophages (Kobayashi et al, 2015); its application on macrophage‐related diseases such as trigeminal nerve pain (Batbold et al, 2017; Kanno et al, 2020), inflammatory bowel disease (Tian et al, 2021), and endometriosis (Sekiguchi et al, 2019) has been attempted. We have demonstrated that clophosome treatment inhibits activated SCs/GERCs with macrophage phenotypes, thereby enabling HC protection during viral infection, implying the possibility of using this compound to treat SSHL (Hayashi et al, 2021).…”