ER-to-Golgi protein transport involves transport vesicles of which formation is initiated by assembly of Sar1. The assembly of Sar1 is suppressed by protein kinase inhibitor H89, suggesting that ER-to-Golgi transport is regulated progressively by H89 sensitive kinase. ER-resident G(i2) protein suppresses vesicle formation with inhibition of Sar1 assembly. This study ...

Background and purpose.  Airway remodelling is a consequence of long-terminflammation and mitogen-activated protein kinases (MAPKs) are key signalling molecules that drive pro-inflammatory pathways. The endogenous MAPK deactivator-MAPK phosphatase 1 (MKP-1) - is a critical negative regulator of the myriad pro-inflammatory pathways activated by MAPKs in the airway. Herein we investigate ...

IL (interleukin)-6, which was originally identified as a B-cell differentiation factor, is a multifunctional cytokine that regulates the immune response, haemopoiesis, the acute phase response and inflammation. IL-6 is produced by various types of cell and influences various cell types, and has multiple biological activities through its unique receptor system. ...

Inhibition of signal transduction pathways has been successfully introduced into cancer treatment. The dual phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor NVP-BEZ235 has antitumor activity in vitro against solid tumors. Here, we examined the activity of NVP-BEZ235 in acute lymphoblastic leukemia (ALL) cells and the best modalities ...

Phosphorylation of the cAMP response element binding protein (CREB) by cAMP-dependent kinase (PKA) is critical to memory formation. However, activation of PKA can also increase tau phosphorylation, which may contribute to memory impairment. Therefore, the regulation of PKA may be part of the mechanism by which glucocorticoids (GCs) influence memory. ...

C-type lectin receptors (CLRs) that couple with the kinase Syk are major pattern recognition receptors for the activation of innate immunity and host defense. CLRs recognize fungi and other forms of microbial or sterile danger, and they induce inflammatory responses through the adaptor protein Card9. The mechanisms relaying CLR proximal ...

The aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS). The new class of anti-type 2 diabetes drugs, dipeptidyl peptidase-4 inhibitors, improves glucose metabolism by increasing levels of active glucagon-like peptide (GLP)-1. Endothelial function was examined by acetylcholine-induced endothelium-dependent vasorelaxation using aortic ...

Reduction of lung inflammation is one of the goals of cystic fibrosis (CF) therapy. Among anti-inflammatory molecules, glucocorticoids (GC) are one of the most prescribed. However, CF patients seem to be resistant to glucocorticoid treatment. Several molecular mechanisms that contribute to decrease anti-inflammatory effects of glucocorticoids have been identified in ...

Although fisetin, a natural flavonoid, was known to inhibit proliferation, carcinogenesis and inflammation, the underlying anti-inflammatory mechanism of fistein still remains unclear. Thus, in the present study, the anti-inflammatory mechanism of fisetin was investigated in association with mitogen-activated protein kinase (MAPK) and nuclear factor κ B (NF-κB) pathways in lipopolysaccharide ...

Microglial cells play a critical role in mediating central nervous system inflammatory processes. Activated microglial cells induced by proinflammatory factor, such as lipopolysaccharide (LPS), release many kinds of neurotoxic cytokines including reactive oxygen species (ROS) which contributes to the pathogenesis of neurodegenerative diseases. Puerarin, extracted from kudzu root, possesses the ...

Signal transducer and activator of transcription 3 (STAT3) is a latent cytoplasmic transcription factor. It is activated by cytokines, including interleukin-6 (IL-6) through phosphorylation at Tyr705 (pY705), which is required for its dimerization and nuclear translocation. However, the role of Ser727 phosphorylation, occurring during activation, remains poorly understood. Using a ...

Phytochemical investigation of Leonurus japonicus has led to the isolation of a labdane diterpene derivative, 15,16-epoxy-3α-hydroxylabda-8,13(16),14-trien-7-one (1), which was tested for its in vitro anti-inflammatory effects. The results demonstrated that 1 exhibits an inhibitory effect on LPS-stimulated RAW 264.7 macrophages. The anti-inflammatory action shown by 1 suppressed LPS-induced NF-κB activation, ...

As an attempt to search for bioactive natural products exerting anti-inflammatory activity, we have evaluated the anti-inflammatory effects of euscaphic acid (19α-hydroxyursane-type triterpenoids, EA) isolated from roots of Rosa rugosa and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. EA concentration-dependently reduced the production of nitric oxide (NO), ...

The mechanism for activation of extracellular transglutaminase 2 (TG2) in the small intestine remains a fundamental mystery in our understanding of celiac sprue pathogenesis. Using the T84 human enterocytic cell line, we show that interferon-γ (IFN-γ), the predominant cytokine secreted by gluten-reactive T cells in the celiac intestine, activates extracellular ...

In this study, we investigated the effects and the protective mechanism of ginsenoside Rd (GRd) which has been identified as one of the effective compounds from ginseng on relapsing colitis model induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. After inducing relapsing colitis in experimental rats on two occasions by intracolonic ...

Secretion of proinflammatory cytokines by LPS activated endothelial cells contributes substantially to the pathogenesis of sepsis. However, the mechanism involved in this process is not well understood. In the present study, we determined the roles of GEF-H1 (guanine-nucleotide exchange factor-H1)-RhoA signaling in LPS-induced interleukin-8 (IL-8, CXCL8) production in endothelial cells. ...

Stringent control of NF-κB and mitogen-activated protein kinase (MAPK) signaling is critical during innate immune responses. TGF-β activated kinase-1 (TAK1) is essential for NF-κB activation in T and B cells but has precisely the opposite activity in myeloid cells. Specific deletion of TAK1 (Map3k7(ΔM/ΔM)) led to development of splenomegaly and ...

Monocyte chemoattractant protein-1 (MCP-1) is an essential cytokine for the migration of monocytes into vessels, and is also involved in the pathogenesis of atherosclerosis. In this study, we investigated the importance of janus kinase 2 (JAK2) and the function of the Akt and glycogen synthase kinase-3β (GSK3β) pathway in toll-like receptor ...

Background and Purpose: Microglial activation plays an important role in neurodegenerative diseases by producing an array of proinflammatory enzymes and cytokines. Ginsenoside Rg1 (Rg1), a well-known Chinese herbal medicine, has been well recognized for its anti-inflammatory effect. This study sought to determine the anti-inflammatory effects of Rg1and its underlying mechanisms ...

Lymphocyte activation and fine tuning of downstream signaling circuits for the regulation of cytokine expression are critical for a successful immune response. Hence, technical protocols permitting simultaneous testing of these attributes in peripheral blood lymphocytes are of paramount importance. Phospho-specific flow cytometry is a novel methodology that detects phosphorylation of ...

Type I interferons (IFN-α/β) have been widely used in the treatment of many viral and malignant diseases by activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway, but the side effects of protein-based IFN therapy severely limit their clinical use. Discovering small molecules to activate the ...

IL-31 is a pruritogenic cytokine, and IL-33 is an alarmin for damaging inflammation. They together relate to the pathogenesis of atopic dermatitis (AD). Eosinophil infiltration into the inner dermal compartment is a predominant pathological feature of AD. We herein investigated the in vitro inflammatory effects of IL-31 and IL-33 on ...

The E3 ubiquitin ligase Pellino 1 can be interconverted between inactive and active forms by a reversible phosphorylation mechanism. In vitro, phosphorylation and activation can be catalysed by either the IRAKs [IL (interleukin)-1-receptor-associated kinases] IRAK1 and IRAK4, or the IKK {IκB [inhibitor of NF-κB (nuclear factor κB)] kinase}-related kinases [IKKϵ ...

Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP ...

Evidence has suggested that insulin resistance (IR) or high levels of glucocorticoids (GCs) may be linked with the pathogenesis and/or progression of Alzheimer's disease (AD). Although studies have shown that a high level of GCs results in IR, little is known about the molecular details that link GCs and IR ...

Engagement of tumor necrosis factor receptor 1 signals two diametrically opposed pathways: survival-inflammation and cell death. An additional switch decides, depending on the cellular context, between caspase-dependent apoptosis and RIP kinase (RIPK)-mediated necrosis, also termed necroptosis. We explored the contribution of both cell death pathways in TNF-induced systemic inflammatory response ...

Abstract Despite defenses by polymorphonuclear neutrophils in the host against invading agents, overproduction of oxidant species by phagocytes can lead to damage in the surrounding tissues. Several benzophenones have been shown to possess anti-inflammatory properties. The effect of the natural benzophenone 7-epiclusianone isolated from leaves of Garcinia brasiliensis was investigated ...

OBJECTIVE: Indirubin-3-monoxime (I3M), an indirubin analogue that shows favorable inhibitory activity targeting cyclin-dependent kinase and glycogen synthase kinase, exhibits various biological properties, including chemopreventive, antiangiogenic, and neuropreventive activities. In the present study, we investigated the ability of I3M to regulate inflammatory reactions in macrophages. METHODS: The effects of I3M on ...

The interferon (IFN) system is integral to the host response against viruses to which many viruses have developed strategies to overcome its antiviral effects. The effects of hepatitis E virus (HEV), the causative agent of hepatitis E, on IFN signaling have not been investigated primarily because of the non-availability of ...

Toll like receptors (TLRs) use Toll-IL-1 receptor (TIR) domain-containing adapters, such as myeloid differentiation primary response gene 88 (MyD88) and TIR domain-containing adapter inducing IFN-β (TRIF), to induce activation of transcription factors, including NF-κB, MAP kinases, and IFN regulatory factors. TLR signaling also leads to activation of PI3K, but the ...

Toll-like receptors (TLRs) recognize pathogens and their components, thereby initiating immune responses to infectious organisms. TLR ligation leads to the activation of NF-κB and MAPKs through well-defined pathways, but it has remained unclear how TLR signaling activates PI3K, which provides an inhibitory pathway limiting TLR responses. Here, we show that ...

Ampelopsin (AMP), a plant flavonoid, has potent anti-inflammatory properties in vitro and in vivo. The molecular mechanisms of ampelopsin on pharmacological and biochemical actions of RAW264.7 macrophages in inflammation have not been clearly elucidated yet. In the present study, non-cytotoxic level of ampelopsin significantly inhibited the release of nitric oxide ...

Airway smooth muscle (ASM) plays an important immunomodulatory role in airway inflammation in asthma. In our previous in vitro studies in ASM cells delineating the pro-inflammatory mitogen-activated protein kinase (MAPK) signaling pathways activated by tumor necrosis factor α (TNFα), we observed that TNFα concomitantly induces the rapid, but transient, upregulation ...

The STAT6 (signal transducer and activator of transcription 6) protein facilitates T-helper cell 2 (Th2) mediated responses that control IgE-mediated atopic diseases such as asthma. We have identified compounds that bind to STAT6 and inhibit STAT6 tyrosine phosphorylation induced by IL-4. In the bronchial epithelial cell line BEAS-2B, compound (R)-84 ...

Compartmentalization of nucleic acid sensing TLR9 has been implicated as a mechanism to prevent recognition of self nucleic acid structures. Furthermore, recognition of CpG DNA in different endosomal compartments leads to the production of the proinflammatory cytokine TNF-α, or type I IFN. We previously characterized a tyrosine-based motif at aa ...

AIM OF THE STUDY: Polygonum hydropiper L. (Polygonaceae) has been traditionally used to treat various inflammatory diseases such as rheumatoid arthritis. However, no systematic studies on the anti-inflammatory actions of Polygonum hydropiper and its inhibitory mechanisms have been reported. This study is therefore aimed at exploring the anti-inflammatory effects of ...

Morchella conica is a species of rare edible mushroom whose multiple medicinal functions have been proven. However, reports barely mention the mechanisms of these functions. In this study, the effects of two polysaccharides from M. conica (PMCs) on nitric oxide (NO) production in lipopolysaccharide (LPS)-treated macrophages were investigated. The results ...

AIM OF STUDY: Cinnamomum cassia Blume (Aceraceae) has been traditionally used to treat various inflammatory diseases such as gastritis. However, the anti-inflammatory mechanism of Cinnamomum cassia has not been fully elucidated. This study examined the anti-inflammatory mechanism of 95% ethanol extract (Cc-EE) of Cinnamomum cassia. MATERIALS AND METHODS: The effect ...

Inflammatory bowel disease is characterized by dysregulated immune responses against intestinal microflora leading to marked activation of nuclear factor-κB (NF-κB) with subsequent production of pro-inflammatory cytokines. Besides NF-κB, the tumor progression locus 2 (TPL-2)/extracellular signal-regulated kinase (ERK) pathway also regulates inflammatory cytokines such as interleukin-1β and tumor necrosis factor-α, but ...

Cystatin B and signal transducer and activator of transcription-1 (STAT-1) phosphorylation have recently been shown to increase human immunodeficiency virus-1 (HIV-1) replication in monocyte-derived macrophages (MDM), but the molecular pathways by which they do are unknown. We hypothesized that cystatin B inhibits the interferon (IFN) response and regulates STAT-1 phosphorylation ...

ETHNOPHARMACOLOGICAL RELEVANCE: Gastrodia elata Blume (Orchidaceae, GE) a traditional plant in Oriental countries is known for its enormous benefits to treat headaches, dizziness, vertigo and convulsive illnesses. In the present study, the ethnopharmacological role of GE in neuroinflammation mediated by activated microglia and the mechanisms underlying were reported. MATERIALS AND ...

Citrobacter rodentium (CR) induces transmissible murine colonic hyperplasia (TMCH) and variable degrees of inflammation and necrosis depending upon the genetic background. Utilizing the CR-induced TMCH in C3H/HeNHsd inbred mice, we observed significant crypt hyperplasia on days 3 and 7 preceding active colitis. NF-κB activity in the crypt-denuded lamina propria (CLP) ...

The root of Angelica acutiloba is a widely used herbal medicine which has been used as a typical therapeutic for allergic diseases in traditional medicine. This study was aimed to investigate the effects of A. acutiloba on allergic reactions in in vitro and in vivo models and its mechanism of ...

Abstract The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway plays an important role in cellular responses to cytokines and growth factors. Recent studies have identified a recurrent somatic activating mutation (JAK2 V617F) in majority of patients with myeloproliferative disorders (MPDs). Development of drugs that target JAK2 ...

Lipopolysaccharide (LPS)-stimulated RAW 264.7 cells are commonly used as a model for assessing the anti-inflammatory or chemopreventive potential of test compounds. Epimuqubilin A, a norsesterterpene peroxide isolated from marine sponge Latrunculia sp., inhibits nitric oxide production in LPS-stimulated RAW 264.7 cells (IC(50) = 7.6 µM). At both the mRNA and ...

The aim of this study was to investigate the anti-inflammatory properties of each fraction of Hericium erinaceus (HE). The ethanol extract from HE was partitioned with different solvents in the order of increasing polarity. The treatment with 10-100 μg/mL of each fraction did not reduce RAW 264.7 cell viability except ...

The effect of Lactobacillus plantarum genomic DNA (p-gDNA) on lipopolysaccharide (LPS)-induced mitogen-activated protein kinase (MAPK) activation, nuclear factor-kappa B (NF-κB) activation, and the expressions of tumor necrosis factor-alpha (TNF-α), interleukin-1 receptor-associated kinase M (IRAK-M), and the pattern recognition receptor (PRR) were examined. Pretreatment of p-gDNA inhibited the phosphorylation of MAPKs ...

Jak/STAT is an important signaling pathway mediating multiple events in development. We describe participation of metazoan co-activator SAYP/PHF10 in this pathway downstream of STAT. The latter, via its activation domain, interacts with the conserved core of SAYP. STAT is associated with the SAYP-containing co-activator complex BTFly and recruits BTFly onto ...

Epidemiological studies have associated indoor phthalate exposure with increased incidences and severity of asthma in children and adults, and inflammatory effects have been suggested as a possible mechanism. Recent studies report that phthalates may activate mitogen-activated protein (MAP) kinase p38 and various peroxisome proliferator-activated receptor (PPAR) isoforms. Here we confirm ...

OBJECTIVES: The objective of this study was to investigate the effect of the novel Janus kinase inhibitor CP-690,550 in fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA).METHODS: RA FLSs were isolated from tissue obtained by arthroplasty, cultured and serum-starved 48 h prior to stimulation. Messenger RNA and protein levels ...