scholarly journals Lancemaside A fromCodonopsis lanceolataModulates the Inflammatory Responses Mediated by Monocytes and Macrophages

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Eunji Kim ◽  
Woo Seok Yang ◽  
Ji Hye Kim ◽  
Jae Gwang Park ◽  
Han Gyung Kim ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Morphological Changes ◽  
Costimulatory Molecule ◽  
Raw264.7 Cells ◽  
U937 Cells ◽  
Neutralizing Capacity ◽  
Lancemaside A ◽  
Monocytes And Macrophages

In this study, we aimed to examine the cellular and molecular mechanisms of lancemaside A fromCodonopsis lanceolata(Campanulaceae) in the inflammatory responses of monocytes (U937 cells) and macrophages (RAW264.7 cells). Lancemaside A significantly suppressed the inflammatory functions of lipopolysaccharide- (LPS-) treated RAW264.7 cells by suppressing the production of nitric oxide (NO), the expression of the NO-producing enzyme inducible NO synthase (iNOS), the upregulation of the costimulatory molecule CD80, and the morphological changes induced by LPS exposure. In addition, lancemaside A diminished the phagocytic activity of RAW264.7 cells and boosted the neutralizing capacity of these cells when treated with the radical generator sodium nitroprusside (SNP). Interestingly, lancemaside A strongly blocked the adhesion activity of RAW264.7 cells to plastic culture plates, inhibited the cell-cell and cell-fibronectin (FN) adhesion of U937 cells that was triggered by treatment with an anti-β1-integrin (CD29) antibody and immobilized FN, respectively. By evaluating the activation of various intracellular signaling pathways and the levels of related nuclear transcription factors, lancemaside A was found to block the activation of inhibitor ofκB kinase (IKK) and p65/nuclear factor- (NF-)κB. Taken together, our findings strongly suggest that the anti-inflammatory function of lancemaside A is the result of its strong antioxidative and IKK/NF-κB inhibitory activities.

scholarly journals NF-κB/AP-1-Targeted Inhibition of Macrophage-Mediated Inflammatory Responses by Depigmenting Compound AP736 Derived from Natural 1,3-Diphenylpropane Skeleton

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Van Thai Ha ◽  
Heung Soo Beak ◽  
Eunji Kim ◽  
Kwang-Soo Baek ◽  
Muhammad Jahangir Hossen ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Morphological Changes ◽  
Skin Inflammation ◽  
No Synthase ◽  
Raw264.7 Cells ◽  
Inflammatory Gene Expression ◽  
Anti Inflammatory ◽  
Targeted Inhibition ◽  
Tyrosinase Expression ◽  
Phagocytic Uptake

AP736 was identified as an antimelanogenic drug that can be used for the prevention of melasma, freckles, and dark spots in skin by acting as a suppressor of melanin synthesis and tyrosinase expression. Since macrophage-mediated inflammatory responses are critical for skin health, here we investigated the potential anti-inflammatory activity of AP736. The effects of AP736 on various inflammatory events such as nitric oxide (NO)/prostaglandin (PG) E2production, inflammatory gene expression, phagocytic uptake, and morphological changes were examined in RAW264.7 cells. AP736 was found to strongly inhibit the production of both NO and PGE2in lipopolysaccharide- (LPS-) treated RAW264.7 cells. In addition, AP736 strongly inhibited both LPS-induced morphological changes and FITC-dextran-induced phagocytic uptake. Furthermore, AP736 also downregulated the expression of multiple inflammatory genes, such as inducible NO synthase (iNOS), cyclooxygenase- (COX-) 2, and interleukin- (IL-) 1βin LPS-treated RAW264.7 cells. Transcription factor analysis, including upstream signalling events, revealed that both NF-κB and AP-1 were targeted by AP736 via inhibition of the IKK/IκBαand IRAK1/TAK1 pathways. Therefore, our results strongly suggest that AP736 is a potential anti-inflammatory drug due to its suppression of NF-κB-IKK/IκBαand AP-1-IRAK1/TAK1 signalling, which may make AP736 useful for the treatment of macrophage-mediated skin inflammation.

scholarly journals CD58 Immunobiology at a Glance

2021 ◽  
Vol 12 ◽  
Author(s):  
Yalu Zhang ◽  
Qiaofei Liu ◽  
Sen Yang ◽  
Quan Liao
Keyword(s):  
Nk Cells ◽  
Intracellular Signaling ◽  
Inflammatory Responses ◽  
Nk Cell ◽  
Costimulatory Molecule ◽  
Soluble Form ◽  
Target Cells ◽  
Lymphocyte Function

The glycoprotein CD58, also known as lymphocyte-function antigen 3 (LFA-3), is a costimulatory receptor distributed on a broad range of human tissue cells. Its natural ligand CD2 is primarily expressed on the surface of T/NK cells. The CD2-CD58 interaction is an important component of the immunological synapse (IS) that induces activation and proliferation of T/NK cells and triggers a series of intracellular signaling in T/NK cells and target cells, respectively, in addition to promoting cell adhesion and recognition. Furthermore, a soluble form of CD58 (sCD58) is also present in cellular supernatant in vitro and in local tissues in vivo. The sCD58 is involved in T/NK cell-mediated immune responses as an immunosuppressive factor by affecting CD2-CD58 interaction. Altered accumulation of sCD58 may lead to immunosuppression of T/NK cells in the tumor microenvironment, allowing sCD58 as a novel immunotherapeutic target. Recently, the crucial roles of costimulatory molecule CD58 in immunomodulation seem to be reattracting the interests of investigators. In particular, the CD2-CD58 interaction is involved in the regulation of antiviral responses, inflammatory responses in autoimmune diseases, immune rejection of transplantation, and immune evasion of tumor cells. In this review, we provide a comprehensive summary of CD58 immunobiology.

scholarly journals Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6073
Author(s):  
Laily Rahmawati ◽  
Nur Aziz ◽  
Jieun Oh ◽  
Yo Han Hong ◽  
Byoung Young Woo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Raw264.7 Cells ◽  
Acute Gastritis ◽  
Anti Inflammatory

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.

scholarly journals Host tissue proteomics reveal insights into the molecular basis of Schistosoma haematobium-induced bladder pathology

2021 ◽  
Author(s):  
Derick N. M. Osakunor ◽  
Kenji Ishida ◽  
Olivia K Lamanna ◽  
Mario Rossi ◽  
Michael H Hsieh
Keyword(s):  
Stress Responses ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Morphological Changes ◽  
Protein Translation ◽  
Health Concern ◽  
Disease Manifestation ◽  
Urogenital Schistosomiasis ◽  
Proteome Profiling ◽  
Egg Deposition

Background: Urogenital schistosomiasis remains a major public health concern worldwide. In response to egg deposition, the host bladder undergoes gross and molecular morphological changes relevant for disease manifestation. However, limited mechanistic studies to date imply that the molecular mechanisms underlying pathology have not been well-defined. We leveraged a mouse model of urogenital schistosomiasis to perform for the first time, proteome profiling of the early molecular events that occur in the bladder after exposure to S. haematobium eggs, and to elucidate the protein pathways involved in urogenital schistosomiasis-induced pathology. Methods: Purified S. haematobium eggs or control vehicle were microinjected into the bladder walls of mice. Mice were sacrificed seven days post-injection and bladder proteins isolated and processed for proteome profiling using mass spectrometry. Results: We demonstrate that biological processes including carcinogenesis, immune and inflammatory responses, increased protein translation or turnover, oxidative stress responses, reduced cell adhesion and epithelial barrier integrity, and increased glucose metabolism were significantly enriched in S. haematobium infection. Conclusion: S. haematobium egg deposition in the bladder results in significant changes in proteins and pathways that play a role in pathology. Our findings highlight the potential bladder protein indicators for host-parasite interplay and provide new insights into the complex dynamics of pathology and characteristic bladder tissue changes in urogenital schistosomiasis. The findings will be relevant for development of improved interventions for disease control.

scholarly journals Native and aspirin-triggered lipoxins control innate immunity by inducing proteasomal degradation of TRAF6

2008 ◽  
Vol 205 (5) ◽  
pp. 1077-1086 ◽  
Author(s):  
Fabiana S. Machado ◽  
Lísia Esper ◽  
Alexandra Dias ◽  
Rajat Madan ◽  
YuanYuan Gu ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Interleukin 1 ◽  
Proteasomal Degradation ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
Immune Signaling ◽  
Innate Immune Signaling

Innate immune signaling is critical for the development of protective immunity. Such signaling is, perforce, tightly controlled. Lipoxins (LXs) are eicosanoid mediators that play key counterregulatory roles during infection. The molecular mechanisms underlying LX-mediated control of innate immune signaling are of interest. In this study, we show that LX and aspirin (ASA)-triggered LX (ATL) inhibit innate immune signaling by inducing suppressor of cytokine signaling (SOCS) 2–dependent ubiquitinylation and proteasome-mediated degradation of TNF receptor–associated factor (TRAF) 2 and TRAF6, which are adaptor molecules that couple TNF and interleukin-1 receptor/Toll-like receptor family members to intracellular signaling events. LX-mediated degradation of TRAF6 inhibits proinflammatory cytokine production by dendritic cells. This restraint of innate immune signaling can be ablated by inhibition of proteasome function. In vivo, this leads to dysregulated immune responses, accompanied by increased mortality during infection. Proteasomal degradation of TRAF6 is a central mechanism underlying LX-driven immune counterregulation, and a hitherto unappreciated mechanism of action of ASA. These findings suggest a new molecular target for drug development for diseases marked by dysregulated inflammatory responses.

scholarly journals The Molecular Mechanisms Underlying the Proinflammatory Actions of Thiazolidinediones in Human Macrophages

2007 ◽  
Vol 21 (8) ◽  
pp. 1756-1768 ◽  
Author(s):  
Julie M. Hall ◽  
Donald P. McDonnell
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Systemic Exposure ◽  
Receptor Subtype ◽  
Peroxisome Proliferator ◽  
Independent Manner ◽  
Subtype Specificity ◽  
Monocytes And Macrophages ◽  
Peroxisome Proliferator Activated Receptors

Abstract It is hypothesized that the antiinflammatory actions of peroxisome proliferator-activated receptors (PPARs) may explain the protective effect of these receptors in diabetes, atherosclerosis, cancer, and other inflammatory diseases. However, emerging evidence for proinflammatory activities of activated PPARs is concerning in light of new studies that associate PPAR modulators with an increased incidence of both cardiovascular events in humans and the sporadic formation of tumors in rodents. In an attempt to define the role of each PPAR subtype in inflammation, we made the unexpected observation that human PPARδ is a positive regulator of inflammatory responses in both monocytes and macrophages. Notably, TNFα-stimulated cells administered PPARδ agonists express and secrete elevated levels of inflammatory cytokines. Most surprising, however, was the finding that thiazolidinediones (TZDs) and other known PPARγ ligands display different degrees of proinflammatory activities in a PPARγ- and PPARα-independent manner via their ability to augment PPARδ signaling. A series of mechanistic studies revealed that TZDs, at clinically relevant concentrations, bind and activate the transcriptional activity of PPARδ. Collectively, these studies suggest that the observed proinflammatory and potentially deleterious effects of PPARγ ligands may be mediated through an off-target effect on PPARδ. These studies highlight the need for PPAR modulators with increased receptor subtype specificity. Furthermore, they suggest that differences in systemic exposure and consequently in the activation of PPARγ and PPARδ may explain why TZDs can exhibit both inflammatory and antiinflammatory activities in humans.

scholarly journals Molecular Mechanism of Macrophage Activation by Red Ginseng Acidic Polysaccharide from Korean Red Ginseng

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Se Eun Byeon ◽  
Jaehwi Lee ◽  
Ji Hye Kim ◽  
Woo Seok Yang ◽  
Yi-Seong Kwak ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Intracellular Signaling ◽  
Morphological Changes ◽  
Target Surface ◽  
Raw264.7 Cells ◽  
No Production ◽  
Mrna Levels ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Acidic Polysaccharide

Red ginseng acidic polysaccharide (RGAP), isolated from Korean red ginseng, displays immunostimulatory and antitumor activities. Even though numerous studies have been reported, the mechanism as to how RGAP is able to stimulate the immune response is not clear. In this study, we aimed to explore the mechanism of molecular activation of RGAP in macrophages. RGAP treatment strongly induced NO production in RAW264.7 cells without altering morphological changes, although the activity was not strong compared to LPS-induced dendritic-like morphology in RAW264.7 cells. RGAP-induced NO production was accompanied with enhanced mRNA levels of iNOS and increases in nuclear transcription factors such as NF-κB, AP-1, STAT-1, ATF-2, and CREB. According to pharmacological evaluation with specific enzyme inhibitors, Western blot analysis of intracellular signaling proteins and inhibitory pattern using blocking antibodies, ERK, and JNK were found to be the most important signaling enzymes compared to LPS signaling cascade. Further, TLR2 seems to be a target surface receptor of RGAP. Lastly, macrophages isolated from RGS2 knockout mice or wortmannin exposure strongly upregulated RGAP-treated NO production. Therefore, our results suggest that RGAP can activate macrophage function through activation of transcription factors such as NF-κB and AP-1 and their upstream signaling enzymes such as ERK and JNK.

The Mechanisms Behind the Biological Activity of Flavonoids

2019 ◽  
Vol 26 (39) ◽  
pp. 6976-6990 ◽  
Author(s):  
Ana María González-Paramás ◽  
Begoña Ayuda-Durán ◽  
Sofía Martínez ◽  
Susana González-Manzano ◽  
Celestino Santos-Buelga
Keyword(s):  
Gene Expression ◽  
Biological Activity ◽  
Phenolic Compounds ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Radical Scavenging ◽  
Model Organism ◽  
Stress Theory ◽  
Radical Scavenging Properties

: Flavonoids are phenolic compounds widely distributed in the human diet. Their intake has been associated with a decreased risk of different diseases such as cancer, immune dysfunction or coronary heart disease. However, the knowledge about the mechanisms behind their in vivo activity is limited and still under discussion. For years, their bioactivity was associated with the direct antioxidant and radical scavenging properties of phenolic compounds, but nowadays this assumption is unlikely to explain their putative health effects, or at least to be the only explanation for them. New hypotheses about possible mechanisms have been postulated, including the influence of the interaction of polyphenols and gut microbiota and also the possibility that flavonoids or their metabolites could modify gene expression or act as potential modulators of intracellular signaling cascades. This paper reviews all these topics, from the classical view as antioxidants in the context of the Oxidative Stress theory to the most recent tendencies related with the modulation of redox signaling pathways, modification of gene expression or interactions with the intestinal microbiota. The use of C. elegans as a model organism for the study of the molecular mechanisms involved in biological activity of flavonoids is also discussed.

Resolution-Associated Molecular Patterns (RAMPs) as Endogenous Regulators of Glia Functions in Neuroinflammatory Disease

2020 ◽  
Vol 19 (7) ◽  
pp. 483-494
Author(s):  
Tyler J. Wenzel ◽  
Evan Kwong ◽  
Ekta Bajwa ◽  
Andis Klegeris
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Bioactive Lipids ◽  
Prothymosin Α ◽  
Neuroinflammatory Disease ◽  
Cellular Debris ◽  
Αb Crystallin ◽  
Endogenous Regulators ◽  
The Central Nervous System ◽  
Molecular Patterns

: Glial cells, including microglia and astrocytes, facilitate the survival and health of all cells within the Central Nervous System (CNS) by secreting a range of growth factors and contributing to tissue and synaptic remodeling. Microglia and astrocytes can also secrete cytotoxins in response to specific stimuli, such as exogenous Pathogen-Associated Molecular Patterns (PAMPs), or endogenous Damage-Associated Molecular Patterns (DAMPs). Excessive cytotoxic secretions can induce the death of neurons and contribute to the progression of neurodegenerative disorders, such as Alzheimer’s disease (AD). The transition between various activation states of glia, which include beneficial and detrimental modes, is regulated by endogenous molecules that include DAMPs, cytokines, neurotransmitters, and bioactive lipids, as well as a diverse group of mediators sometimes collectively referred to as Resolution-Associated Molecular Patterns (RAMPs). RAMPs are released by damaged or dying CNS cells into the extracellular space where they can induce signals in autocrine and paracrine fashions by interacting with glial cell receptors. While the complete range of their effects on glia has not been described yet, it is believed that their overall function is to inhibit adverse CNS inflammatory responses, facilitate tissue remodeling and cellular debris removal. This article summarizes the available evidence implicating the following RAMPs in CNS physiological processes and neurodegenerative diseases: cardiolipin (CL), prothymosin α (ProTα), binding immunoglobulin protein (BiP), heat shock protein (HSP) 10, HSP 27, and αB-crystallin. Studies on the molecular mechanisms engaged by RAMPs could identify novel glial targets for development of therapeutic agents that effectively slow down neuroinflammatory disorders including AD.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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