Liraglutide Exerts Potential Anti-inflammatory Effect in Type 1 Diabetes by Inhibiting IFN-γ Production via Suppressing JAK-STAT Pathway

Zhao, Yunjuan; Xie, Yunliang; Li, Wangen

doi:10.2174/1871530319666190301115654

Cited by 6 publications

(3 citation statements)

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“…In non-obese diabetic (NOD) mice which are a murine model of T1DM, GLP-1RAs can improve immune functions and inflammatory responses as well as mitigating against islet cell damage, an action which may be related to the decrease in the expression of miR-19b [145]. Similarly, GLP-1RAs exert the potential protection against inflammatory responses in T1DM through decreasing IFN-γ secretion and downregulating PD-1 expression in T cells by attenuating the Janus kinase (JAK)-STAT pathway [146,147]. Thus, GLP-1RAs play an underlying role in immune-regulation in T1DM (Figure 2).…”

Section: Modulating Immune Cell Function and Inflammation By Glp-1rasmentioning

confidence: 99%

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

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Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.

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Section: Modulating Immune Cell Function and Inflammation By Glp-1rasmentioning

confidence: 99%

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Ma¹,

Liu²,

Ilyas³

et al. 2021

Int. J. Biol. Sci.

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“…CD4 + T cells can differentiate into different subtypes, among which helper T cells (Th), Th1 cells and Th17 cells are pro-inflammatory cells, while Th2 cells and regulatory T cells (Tregs) are anti-inflammatory cells 33 – 35 . CD4 + T cell subtypes and their secreted cytokines play an important role in T 1 DM 23 , 36 , 37 . The ratio of Th1 and Th17 cells in T1DM patients increases, and the expression of pro-inflammatory factors such as IL-17A, IFN-γ, and IL-2 secreted by them is up-regulated, which aggravates the inflammatory response in the body, and the ratio and function of Tregs cells are weakened, and the expression of anti-inflammatory factors such as IL-10 and TGF-β is down-regulated, leading to a decrease in the body's ability to suppress inflammation 38 – 40 .…”

Section: Discussionmentioning

confidence: 99%

Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice

Gao

Jiang

et al. 2022

Sci Rep

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Immune cells play an important role in the development of inflammation in type 1 diabetes mellitus, so we want to explore the changes of CD4+ T cells and macrophages in vivo, which can provide an experimental basis for immunotherapy based on CD4+ T cells and macrophages. The intraperitoneal injection of streptozocin was used to induce a type 1 diabetes mellitus mouse model; the blood glucose, body weight, and the expression of inflammatory factors in the kidney were measured. Immunohistochemistry was applied to determine and analyze the infiltration of CD4+ T cells and macrophages in the spleen, pancreas, and kidney. The subtypes of macrophages in the kidney and CD4+ T cells in the spleen were analyzed by flow cytometry. Our study suggests that CD4+ T cells and macrophages increase, while the inflammatory immune response system is activated in the development of T1DM. CD4+ T cells positively correlated with macrophages in the pancreas and kidney of T1DM. CD4+ T cells turn to pro-inflammatory subtypes in the spleen of T1DM, while macrophages turn to pro-inflammatory subtypes in the kidney of T1DM. Therefore, regulation of CD4+ T cells and macrophages may be a potential target for T1DM and kidney complications.

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“…Since IL-2 signaling can be transduced through 3 different signaling pathways (the JAK-STAT, PI3K/Akt/mTOR, and MAPK/ERK pathways), IL-2 versatility can be achieved [29]. After costimulation with CD28, the optimal activity of IL-2 and these pathways is induced, and IFN-c can also activate multiple signaling pathways, the most common of which is the JAK-STAT pathway [30][31][32] .…”

Section: E In Vivo Killing Mechanism Of Ctlsmentioning

confidence: 99%

GP96 and SMP30 Protein Priming of Dendritic Cell Vaccination Induces a More Potent CTL Response against Hepatoma

Huang

Pan

Zhang

et al. 2022

Journal of Healthcare Engineering

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Heat-shock protein (HSP) GP96 is a well-known adjuvant in immunotherapy. It belongs to the HSP90 family. Our previous study demonstrated that DC pulsed with recombinant senescence marker protein 30 (SMP30) could induce cytotoxic T lymphocytes (CTLs) against liver cancer cells in vitro. In this study, SMP30 and GP96 were subcloned into lentiviruses and transfected into DCs from healthy donors. We included six groups: the GP96-SMP30 group, GP96 group, SMP30 group, DC group, empty vector control group, and hepatoma extracted protein group. We used ELISA to detect cytokines and flow cytometry to assess CD80 and CD86 on DCs and the effect of CTLs. Our vector design was considered successful and further studied. In the SMP30 group, DC expresses more CCR7 and CD86 than the control group; in the SMP30+GP96 group, DC express more CCR7, CD86, and CD80 than the control group. Transfected DCs secreted more TNF-α and interferon-β and induced more CTLs than control DCs. SMP30 + GP96 effectively stimulated the proliferation of T cells compared with control treatment ( P < 0.01). We detected the cytokines TNF-α, TNF-β, IL-12, and IFN (α, β, and γ) via ELISA (Figure 5) and verified the killing effect via FCM. Four E : T ratios (0 : 1, 10 : 1, 20 : 1, and 40 : 1) were tested. The higher the ratio was, the better the effects were. We successfully constructed a liver cancer model and tested the CTL effect in each group. The GP96 + SMP30 group showed a better effect than the other groups. GP96 and SMP30 can stimulate DCs together and produce more potent antitumor effects. Our research may provide a new efficient way to improve the therapeutic effect of DC vaccines in liver cancer.

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Liraglutide Exerts Potential Anti-inflammatory Effect in Type 1 Diabetes by Inhibiting IFN-γ Production via Suppressing JAK-STAT Pathway

Cited by 6 publications

References 0 publications

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

Changes of macrophage and CD4+ T cell in inflammatory response in type 1 diabetic mice

GP96 and SMP30 Protein Priming of Dendritic Cell Vaccination Induces a More Potent CTL Response against Hepatoma

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