Centipeda minima Extract Attenuates Dextran Sodium Sulfate-Induced Acute Colitis in Mice by Inhibiting Macrophage Activation and Monocyte Chemotaxis

Inflammatory bowel disease (IBD) is an idiopathic inflammatory disease affecting the gastrointestinal tract. IBD is characterized by courses of relapse and remission, and remains incurable. Although multiple factors are related to the pathogenesis of IBD, disruption of intestinal mucosa homeostasis has been proposed to be a major contributor to IBD, and abnormal activation of immune cells is key for initiation of the inflammatory response. Macrophages are the most abundant immune cells in the intestine. Once activated, they are responsible for secretion of pro-inflammatory cytokines and chemokines to attract circulating monocytes to inflammatory sites, exacerbating the inflammatory response, and leading to tissue damage. Therefore, the suppression of activated macrophages, cytokine/chemokine production, and subsequent monocyte chemotaxis possesses great potential for the treatment of IBD. In our study, we have demonstrated the inhibitory effect of Centipeda minima total extract (CME) on the activation of NF-κB, STAT3, and MAPK signaling in LPS-stimulated RAW264.7 macrophages. In addition, we identified the significant suppressive effect of CME on CCL8 expression in activated macrophages, which potentially contributed to inhibition of monocyte chemotaxis. In the DSS-induced acute colitis mouse model, we have demonstrated the suppressive effect of CME on intestinal macrophage infiltration and its ameliorative effect in IBD. Altogether, we have provided evidence of the therapeutic effect of CME in IBD and the potential of CME for the treatment of IBD.

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Momordica charantia Suppresses Inflammation and Glycolysis in Lipopolysaccharide-Activated RAW264.7 Macrophages

Molecules ◽

10.3390/molecules25173783 ◽

2020 ◽

Vol 25 (17) ◽

pp. 3783

Author(s):

Shi Yan Lee ◽

Won Fen Wong ◽

Jiyang Dong ◽

Kian-Kai Cheng

Keyword(s):

Glucose Metabolism ◽

Inflammatory Response ◽

Macrophage Activation ◽

Nuclear Translocation ◽

Lactate Production ◽

Bioactive Compound ◽

Momordica Charantia ◽

Activated Macrophages ◽

Raw264.7 Macrophages ◽

Tnf Α

Macrophage activation is a key event that triggers inflammatory response. The activation is accompanied by metabolic shift such as upregulated glucose metabolism. There are accumulating evidences showing the anti-inflammatory activity of Momordica charantia. However, the effects of M. charantia on inflammatory response and glucose metabolism in activated macrophages have not been fully established. The present study aimed to examine the effect of M. charantia in modulating lipopolysaccharide (LPS)-induced inflammation and perturbed glucose metabolism in RAW264.7 murine macrophages. The results showed that LPS-induced NF-κB (p65) nuclear translocation was inhibited by M. charantia treatment. In addition, M. charantia was found to reduce the expression of inflammatory genes including IL6, TNF-α, IL1β, COX2, iNOS, and IL10 in LPS-treated macrophages. Furthermore, the data showed that M. charantia reduced the expression of GLUT1 and HK2 genes and lactate production (−28%), resulting in suppression of glycolysis. Notably, its effect on GLUT1 gene expression was found to be independent of LPS-induced inflammation. A further experiment also indicated that the bioactivities of M. charantia may be attributed to its key bioactive compound, charantin. Taken together, the study provided supporting evidences showing the potential of M. charantia for the treatment of inflammatory disorders.

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Methamphetamine causes neurotoxicity by promoting polarization of macrophages and inflammatory response

Human & Experimental Toxicology ◽

10.1177/0960327117714039 ◽

2017 ◽

Vol 37 (5) ◽

pp. 486-495 ◽

Cited By ~ 5

Author(s):

X Li ◽

F Wu ◽

L Xue ◽

B Wang ◽

J Li ◽

...

Keyword(s):

Inflammatory Response ◽

Protein Expression ◽

Macrophage Polarization ◽

Enzyme Linked Immunosorbent Assay ◽

Neuronal System ◽

Activated Macrophages ◽

Alternatively Activated Macrophages ◽

Raw264.7 Macrophages ◽

Gene And Protein Expression ◽

Anti Inflammatory

Macrophages, especially their activation state, are closely related to the progression of neurotoxicity. Classically activated macrophages (M1) are proinflammatory effectors, while alternatively activated macrophages (M2) exhibit anti-inflammatory properties. As a powerful addictive psychostimulant drug, coupled with its neurotoxicity, methamphetamine (Meth) abuse may lead to long-lasting abnormalities in the neuronal system. The present study investigated the effect of Meth at subtoxic concentration on macrophage activation state and its underlying toxicity to neuronal cells. PC12 and Murine RAW264.7 cells were coincubated with Meth to test its toxicity. 3-(4,5-Dimethylthiazol)-2,5-diphenyltetrazolium-bromide, enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot assays were performed to evaluate the toxicity, cytokine secretion, gene, and protein expression. Results showed that cytotoxicity was enhanced on PC12 cells after coculturing with RAW264.7 stimulated with Meth. RAW264.7 macrophages tended to switch to the M1 phenotype, releasing more nitric oxide and proinflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin (IL)-12, and IL-1β, while decreasing the release of anti-inflammatory cytokine IL-10 after treatment with Meth. Meth upregulated the gene expression of IL-6, IL-1β, and TNFα and downregulated the expression of Arg-1, IL-10, and KLF4. Meth could also upregulate the protein expression of IL-1β and TNF α and downregulate the expression of Arg-1 and KLF4. However, the abovementioned effects induced by Meth were abolished by the addition of dopamine receptor D3 antagonist. In conclusion, our study demonstrated that Meth promoted macrophage polarization from M0 to M1 and enhanced inflammatory response, which provided the scientific rationale for the neurotoxicity caused by the chronic use of Meth.

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NHE blockade inhibits chemokine production and NF-κB activation in immunostimulated endothelial cells

AJP Cell Physiology ◽

10.1152/ajpcell.00491.2001 ◽

2002 ◽

Vol 283 (2) ◽

pp. C396-C403 ◽

Cited By ~ 50

Author(s):

Zoltán H. Németh ◽

Edwin A. Deitch ◽

Qi Lu ◽

Csaba Szabó ◽

György Haskó

Keyword(s):

Endothelial Cell ◽

Inflammatory Response ◽

Cell Injury ◽

Suppressive Effect ◽

Nuclear Factor ◽

Chemokine Production ◽

Endothelial Cell Injury ◽

Monocyte Chemoattractant ◽

Maximal Activation

Na+/H+exchanger (NHE) activation has been documented to contribute to endothelial cell injury caused by inflammatory states. However, the role of NHEs in regulation of the endothelial cell inflammatory response has not been investigated. The present study tested the hypothesis that NHEs contribute to endothelial cell inflammation induced by endotoxin or interleukin (IL)-1β. NHE inhibition using amiloride, 5-( N-ethyl- N-isopropyl)-amiloride, and 5-( N-methyl- N-isobutyl)amiloride as well as the non-amiloride NHE inhibitors cimetidine, clonidine, and harmaline suppressed endotoxin-induced IL-8 and monocyte chemoattractant protein (MCP)-1 production by human umbilical endothelial vein cells (HUVECs). The suppressive effect of amiloride on endotoxin-induced IL-8 production was associated with a decreased accumulation of IL-8 mRNA. NHE inhibitors suppressed both inhibitory (I)κB degradation and nuclear factor (NF)-κB DNA binding, suggesting that a decrease in activation of the IκB-NF-κB system contributed to the suppression of HUVEC inflammatory response by NHE blockade. NHE inhibition decreased also the IL-1β-induced HUVEC inflammatory response, because amiloride suppressed IL-1β-induced E-selectin expression on HUVECs. These results demonstrate that maximal activation of the HUVEC inflammatory response requires a functional NHE.

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The Immune System Regulation in Sepsis: From Innate to Adaptive

Current Protein and Peptide Science ◽

10.2174/1389203720666190305164128 ◽

2019 ◽

Vol 20 (8) ◽

pp. 799-816 ◽

Cited By ~ 6

Author(s):

Yue Qiu ◽

Guo-wei Tu ◽

Min-jie Ju ◽

Cheng Yang ◽

Zhe Luo

Keyword(s):

Clinical Trials ◽

Immune System ◽

Systemic Inflammatory Response Syndrome ◽

Inflammatory Response ◽

Immune Cells ◽

Current Knowledge ◽

Systemic Inflammatory Response ◽

Immune System Regulation

Sepsis, which is a highly heterogeneous syndrome, can result in death as a consequence of a systemic inflammatory response syndrome. The activation and regulation of the immune system play a key role in the initiation, development and prognosis of sepsis. Due to the different periods of sepsis when the objects investigated were incorporated, clinical trials often exhibit negative or even contrary results. Thus, in this review we aim to sort out the current knowledge in how immune cells play a role during sepsis.

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Upregulation of miR-150-5p alleviates LPS-induced inflammatory response and apoptosis of RAW264.7 macrophages by targeting Notch1

Open Life Sciences ◽

10.1515/biol-2020-0058 ◽

2020 ◽

Vol 15 (1) ◽

pp. 544-552

Author(s):

Xiaoyan Deng ◽

Zhixing Lin ◽

Chao Zuo ◽

Yanjie Fu

Keyword(s):

Inflammatory Response ◽

Underlying Mechanism ◽

Notch Receptor ◽

Raw264.7 Cells ◽

Luciferase Reporter ◽

Raw264.7 Macrophages ◽

Factor Α ◽

Anti Inflammation ◽

Necrosis Factor ◽

Dual Luciferase Reporter Assay

AbstractCirculating miR-150-5p has been identified as a prognostic marker in patients with critical illness and sepsis. Herein, we aimed to further explore the role and underlying mechanism of miR-150-5p in sepsis. Quantitative real-time-PCR assay was performed to detect the expression of miR-150-5p upon stimulation with lipopolysaccharide (LPS) in RAW264.7 cells. The levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-1β were measured by ELISA assay. Cell apoptosis was determined using flow cytometry. Western blot was used to assess notch receptor 1 (Notch1) expression in LPS-induced RAW264.7 cells. Dual-luciferase reporter assay was employed to validate the target of miR-150-5p. Our data showed that miR-150-5p was downregulated and Notch1 was upregulated in LPS-stimulated RAW264.7 cells. miR-150-5p overexpression or Notch1 silencing alleviated LPS-induced inflammatory response and apoptosis in RAW264.7 cells. Moreover, Notch1 was a direct target of miR-150-5p. Notch1 abated miR-150-5p-mediated anti-inflammation and anti-apoptosis in LPS-induced RAW264.7 cells. miR-150-5p alleviated LPS-induced inflammatory response and apoptosis at least partly by targeting Notch1 in RAW264.7 cells, highlighting miR-150-5p as a target in the development of anti-inflammation and anti-apoptosis drugs for sepsis treatment.

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YTHDF2 mediates LPS-induced osteoclastogenesis and inflammatory response via the NF-κB and MAPK signaling pathways

Cellular Signalling ◽

10.1016/j.cellsig.2021.110060 ◽

2021 ◽

pp. 110060

Author(s):

Caihong Fang ◽

Mingli He ◽

Di Li ◽

Qiong Xu

Keyword(s):

Inflammatory Response ◽

Signaling Pathways ◽

Mapk Signaling ◽

Mapk Signaling Pathways

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Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages

International Journal of Molecular Sciences ◽

10.3390/ijms22157856 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7856

Author(s):

Sang Min Lee ◽

Kyung-No Son ◽

Dhara Shah ◽

Marwan Ali ◽

Arun Balasubramaniam ◽

...

Keyword(s):

Molecular Mechanisms ◽

Cytokine Production ◽

Inflammatory Responses ◽

Critical Role ◽

Mapk Signaling ◽

Response To Treatment ◽

No Production ◽

Inflammatory Signaling ◽

Raw264.7 Macrophages ◽

Inflammatory Mediator Production

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.

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600 In vitro anticancer and immunomodulatory activities of NBT-167, a dimer of resveratrol

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0600 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A635-A635

Author(s):

Jeffrey Zhang ◽

Everett Henry ◽

L Harris Zhang ◽

Wanying Zhang

Keyword(s):

T Cells ◽

T Cell ◽

Cancer Cells ◽

Cancer Cell ◽

Immune Cells ◽

Cell Killing ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Raw264.7 Macrophages

BackgroundResveratrol (3,4’,5-trihydroxystilbene), a stilbenoid isolated from many species of plants, is widely known for its antioxidative, anti-inflammatory, immunomodulatory and anticancer activities. Recently, novel resveratrol oligomers have been isolated from various plants; their diverse structures are characterized by the polymerization of two or more resveratrol units. Little is known regarding the anticancer and immunomodulating activities of these oligomers. In this study, we designed in vitro models to compare resveratrol side by side with its natural dimer NBT-167 for their anticancer and immunological activities.MethodsWe isolated resveratrol and its dimer (NBT-167) from plants. The potency of the compounds was compared side by side using cancer cell survival assays and immunological assays with various types of human cells including cancer cell lines, PBMCs and enriched NK, gamma delta T cells, THP-1 monocytic cells, HL-60 promyelocytic leukemia cells as well as mouse RAW264.7 macrophages.ResultsNBT-167 was found to be more potent than resveratrol in inhibiting growth of various cancer cells and modulation of cytokine production from anti-IgM, LPS, PHA or SEB stimulated PBMC. Both compounds similarly enhanced IL-2 stimulated NK and gamma delta T cell killing activity against K562 cells and modulated nitric oxide production from LPS/IFN-g induced RAW264.7 macrophages and phagocytotic activity of HL-60 cells. NBT-167 was slightly more potently than resveratrol in inhibiting chemotaxis of HL-60 cells and blocking cell cycle of THP-1 and HL-60 cells at G1/S transition. In addition, NBT-167, but not resveratrol, could increase IL-2 production and T cell proliferation stimulated with anti-CD3 and anti-CD28 and synergize with anti-PD-1 antibody to increase IL-2 and IFN-gamma production in co-culture of allotypic T cells and dendric cells (MLR).ConclusionsOur data showed that NBT-167, a dimer of resveratrol, had anticancer and immunomodulatory activities such as modulation of expression of cytokines in immune cells and induction of cancer cell-killing activities of NK and gamma delta T cells. Generally, NBT-167 appeared to have higher activities than resveratrol in modulating immune cells and inhibiting cancer cells. NBT-167 could be a promising cancer immunotherapeutic agent targeting both cancer cells and immune cells.

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Inflammasomes inMycobacterium tuberculosis-Driven Immunity

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2017/2309478 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Sebastian Wawrocki ◽

Magdalena Druszczynska

Keyword(s):

Mycobacterium Tuberculosis ◽

Inflammatory Response ◽

Immune Responses ◽

Proinflammatory Cytokines ◽

Immune Cells ◽

Protein Complexes ◽

Inflammasome Activation ◽

Host Immune Responses ◽

Multimeric Protein

The development of effective innate and subsequent adaptive host immune responses is highly dependent on the production of proinflammatory cytokines that increase the activity of immune cells. The key role in this process is played by inflammasomes, multimeric protein complexes serving as a platform for caspase-1, an enzyme responsible for proteolytic cleavage of IL-1βand IL-18 precursors. Inflammasome activation, which triggers the multifaceted activity of these two proinflammatory cytokines, is a prerequisite for developing an efficient inflammatory response against pathogenicMycobacterium tuberculosis(M.tb). This review focuses on the role of NLRP3 and AIM2 inflammasomes inM.tb-driven immunity.

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