The pro-inflammatory effect of triglyceride on human CD4+ T cells and experimental autoimmune uveitis

Tan, Shiyao; Xue, Feng; Liu, Zhangluxi; Wang, Qingfeng; Jiang, Qingyan; Ye, Xingsheng; Li, Hong‐Xi; Su, Guannan; Zhou, Chunjiang; Wang, Yao; Yang, Peizeng

doi:10.1016/j.clim.2022.109056

Cited by 11 publications

(6 citation statements)

References 32 publications

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“…The levels of several inflammatory cytokines closely involved in EAU, such as IFN-γ, IL-17, and TNF-α, were determined. [ 46 – 48 ] As shown in Fig. 3 e-g, stimulation with LPS + IFN-γ increased the levels of these inflammatory factors in PBMCs, whereas treatment with the Fe-curcumin nanozyme decreased these levels.…”

Section: Resultsmentioning

confidence: 87%

Fe-curcumin nanozyme-mediated immunosuppression and anti-inflammation in experimental autoimmune uveitis

Jiang,

Liang,

Gao

et al. 2023

Biomater Res

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Background EAU is an inflammatory disease usually characterized by autoinflammation and autoimmunity and is aggravated by excessive generation of ROS. Conventional hormone therapy often has more adverse effects. It is urgent to find a therapeutic drug with higher efficiency and fewer adverse effects. Methods We developed an Fe-curcumin nanozyme in which natural antioxidants coordinate with Fe3+ to form nanoparticles with excellent solubility for directing anti-inflammatory and ROS scavenging effects to treat EAU. Several experiments were used to detect the characteristics of nanozymes. EAU model rats were used to detect the abilities of decreasing autoinflammation and autoimmunity. PBMCs were used to detect the ability to inhibit cell proliferation. Results Free radical scavenging experiments showed that nanozymes decreased the level of free radicals at low concentrations. In vitro and in vivo experiments revealed that the group treated with Fe-curcumin nanozymes had lower inflammatory reactions and ROS levels than the control group, as reflected by the downregulated levels of several critical inflammatory cytokines, such as IFN-γ, IL-17, and TNF-α; decreased H2O2 release; inhibited proliferation of Th1 and Th17 cells; and alleviated pathological changes in the eye. Importantly, the Fe-curcumin nanozyme was detected in the retina using Prussian blue staining. Additionally, Fe-curcumin nanozyme is noncytotoxic when directing these biological activities. Conclusion This study has demonstrated the feasibility of using the Fe-curcumin nanozyme as a nanodrug to inhibit inflammatory reactions and scavenge ROS in the treatment of EAU, indicating that it may serve as a promising therapeutic agent in clinical treatment. Graphical Abstract

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Section: Resultsmentioning

confidence: 87%

Fe-curcumin nanozyme-mediated immunosuppression and anti-inflammation in experimental autoimmune uveitis

Jiang,

Liang,

Gao

et al. 2023

Biomater Res

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“…Their results demonstrated a distinct lipid metabolite profile, including increased TAG metabolites, in the plasma of patients with active Behçetʼs disease. TAG was able to stimulate the proliferation of CD4+ cells, the expression of IL-17 and IFN-γ by CD4+ T cells as well as Th1 and Th17 cell differentiation in vitro, but did not affect neutrophils [67]. On the other hand, A922500 inhibited TAG generation, ameliorated the severity of EAU, and reduced Th17 frequency and IL-17 expression by CD4+ T cells in vivo.…”

Section: Behçetʼs Diseasementioning

confidence: 93%

“…On the other hand, A922500 inhibited TAG generation, ameliorated the severity of EAU, and reduced Th17 frequency and IL-17 expression by CD4+ T cells in vivo. The proteomics analysis revealed an upregulation of Pik3r2, an apoptosis-related protein, in CD4+ T cells from A922500-treated mice [67].…”

Section: Behçetʼs Diseasementioning

confidence: 97%

“…Since abnormal lipid metabolism plays a role in the inflammation and progression of autoimmune diseases, Tan et al [67] evaluated lipidomic profiles in Behçetʼs disease, as well as the role of triglyceride (TAG) in the pathogenesis of autoimmune uveitis. Their results demonstrated a distinct lipid metabolite profile, including increased TAG metabolites, in the plasma of patients with active Behçetʼs disease.…”

Section: Behçetʼs Diseasementioning

confidence: 99%

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Cytokines in Immune-mediated “Non-infectious” Uveitis

Kalogeropoulos,

Kanavaros,

Vartholomatos

et al. 2023

Klin Monbl Augenheilkd

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Uveitis is a significant cause of ocular morbidity and accounts for approximately 5 – 10% of visual impairments worldwide, particularly among the working-age population. Infections are the cause of ~ 50% cases of uveitis, but it has been suggested that infection might also be implicated in the pathogenesis of immune-mediated “non-infectious” uveitis. There is growing evidence that cytokines (i.e., interleukins, interferons, etc.) are key mediators of immune-mediated “non-infectious” uveitis. For example, activation of the interleukin-23/interleukin-17 signalling pathway is involved in immune-mediated “non-infectious” uveitis. Studies in animal models have been important in investigating the role of cytokines in uveitis. Recent studies of clinical samples from patients with uveitis have allowed the measurement of a considerable array of cytokines even from very small sample volumes (e.g., aqueous and vitreous humour). The identification of complex patterns of cytokines may contribute to a better understanding of their potential pathogenetic role in uveitis as well as to an improved diagnostic and therapeutic approach to treat these potentially blinding pathologies. This review provides further insights into the putative pathobiological role of cytokines in immune-mediated “non-infectious” uveitis.

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“…A922500 also inhibited triglyceride synthesis in plays a therapeutic role in prostate cancer. [ 115 ]. AZD7687 successfully reduced the number of circulating TAG in clinical trials.…”

Section: Lipid Metabolism and Cancer Therapymentioning

confidence: 99%

Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy

Wu,

Pu,

Wang

et al. 2024

Lipids Health Dis

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Lipid metabolism in cancer cells has garnered increasing attention in recent decades. Cancer cells thrive in hypoxic conditions, nutrient deficiency, and oxidative stress and cannot be separated from alterations in lipid metabolism. Therefore, cancer cells exhibit increased lipid metabolism, lipid uptake, lipogenesis and storage to adapt to a progressively challenging environment, which contribute to their rapid growth. Lipids aid cancer cell activation. Cancer cells absorb lipids with the help of transporter and translocase proteins to obtain energy. Abnormal levels of a series of lipid synthases contribute to the over-accumulation of lipids in the tumor microenvironment (TME). Lipid reprogramming plays an essential role in the TME. Lipids are closely linked to several immune cells and their phenotypic transformation. The reprogramming of tumor lipid metabolism further promotes immunosuppression, which leads to immune escape. This event significantly affects the progression, treatment, recurrence, and metastasis of cancer. Therefore, the present review describes alterations in the lipid metabolism of immune cells in the TME and examines the connection between lipid metabolism and immunotherapy.

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The pro-inflammatory effect of triglyceride on human CD4+ T cells and experimental autoimmune uveitis

Cited by 11 publications

References 32 publications

Fe-curcumin nanozyme-mediated immunosuppression and anti-inflammation in experimental autoimmune uveitis

Fe-curcumin nanozyme-mediated immunosuppression and anti-inflammation in experimental autoimmune uveitis

Cytokines in Immune-mediated “Non-infectious” Uveitis

Reprogramming of lipid metabolism in the tumor microenvironment: a strategy for tumor immunotherapy

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