Curcumin Regulated the Homeostasis of Memory T Cell and Ameliorated Dextran Sulfate Sodium-Induced Experimental Colitis

Abstract

Immune memory is protective against reinvasion by pathogens in the homeostatic state, while immune memory disorders can cause autoimmune disease, including inflammatory bowel disease. Curcumin is a natural compound shown to be effective against human inflammatory bowel disease and experimental colitis, but the underlying mechanism is unclear. Here, experimental colitis was induced by dextran sulfate sodium (DSS) in this study. Significant changes in the percentages of naïve, central memory T (TCM), and effector memory (TEM) cells and their CD4+ and CD8+ subsets were found in the peripheral blood of mice with colitis using flow cytometry. After 7 days of continuous curcumin (100 mg/kg/day) administration, the DSS-induced experimental colitis was effectively relieved, with significant decreases in the ratio of day weight to initial body weight, colonic weight, pathological injury score, levels of proinflammatory cytokines IL-7, IL-15, and IL-21, colonic mucosal ulceration, and amount of inflammatory infiltrate. Importantly, curcumin significantly restored the percentages of naïve, TCM, and TEM cells and their CD4+ and CD8+ subpopulations. In addition, curcumin significantly inhibited the activation of the JAK1/STAT5 signaling pathway, downregulation of JAK1, STAT5, and p-STAT5 proteins in colon tissue, and upregulation of PIAS1 proteins. These results suggested that curcumin effectively regulated the differentiation of naïve, TCM, and TEM cells in the peripheral blood to alleviate DSS-induced experimental colitis, which might be related to the inhibition of JAK1/STAT5 signaling activity.

Curcumin Alleviated Dextran Sulfate Sodium-Induced Colitis by Regulating M1/M2 Macrophage Polarization and TLRs Signaling Pathway

“…Mesalazine (batch number: 130407) was purchased from Sunflower Pharma (Jiamusi, China). e doses of curcumin and mesalazine were based on our previous study [18], in which curcumin was added to 1.5% sodium carboxymethylcellulose. e DSS + Cur group was orally administrated with curcumin (100 mg/kg/day) for 14 consecutive days, and the DSS+5-ASA group was orally administrated with mesalazine (300 mg/kg/day), and the Control and DSS groups were given an equal volume of saline, starting from day 8.…”

“…e potential anti-inflammatory effects of curcumin have been extensively studied in various experimental models of IBD over the last decade, including free radical scavenging, antioxidant increase, myeloperoxidase, COX-1, COX-2, LOX, TNF-α, IFN-c, and iNOS inhibition, regulation of multiple signaling pathways, especially kinases (MAPK and ERK) and transcription factors NF-κB [16,17]. Zhong et al also reported that curcumin effectively alleviated DSS-induced colitis, closely related to the regulation of immune memory homeostasis of T cells [18]. However, the modulatory effect of curcumin on M1/M2 macrophages in colitis mice has not been reported.…”

Curcumin regulates the homeostasis of Th17/Treg and improves the composition of gut microbiota in type 2 diabetic mice with colitis

“…When the concentration of blood glucose was higher than 16.7 mmol/L on both occasions (Figure S2a), the DB mice were included in the subsequent experiments. Based on our previous study (Zhong et al, 2020; Zhong et al, 2021), DB mice were given 3% (w/v) DSS solution ad libitum and showed typical clinical symptoms of colitis starting from day 4 of the experiment, with significant weight loss (Figure S2b), anal blood (Figure S2c), generalized tremors and bradycardia, and all died on day 9 (Figure S2d), and post‐mortem examination revealed massive colonic bleeding (Figure S2e). This suggests that diabetes increases susceptibility to colitis in mice and is closely associated with deletion of the leptin receptor gene.…”

“…Before administration, Cur was dissolved in 1.5% (w/v) sodium carboxymethylcellulose (CMC) solution at a dose of 100 mg/kg (purity >95% by HPLC) (Zhong et al, 2020; Zhong et al, 2021). Throughout the experiment, mice in the DSS + Cur and Con+Cur groups were orally administered with 100 mg/kg/day Cur and for 21 consecutive days, and mice in the DSS and Control groups were treated with equal volume of saline.…”

Mechanism of Sishen-Pill-Regulated Special Memory T and mTfh Cell via Involving JAK/STAT5 Pathway in Colitis Mice

“…However, its mechanism is unclear. El-Mahdy and his workmates reported that mesalazine can enhance anti-inflammatory effects to attenuate progression of oxazolone-induced colitis by restoring IL-10 and ZO-1 levels and limiting IL-6/STAT-3 trans-signaling [ 30 , 31 ]. Maybe, these supplied a possible effect to regulate memory T cells in the process of mesalazine treated mice colitis.…”