Abstract NLRP3 is the most crucial member of NLR family, as it detects existence pathogen invasion and self-derived molecules associated with cellular damage. Several studies have reported that excessive inflammasome-mediated caspase-1 activation a key factor in development diseases. Recent Syk involved pathogen-induced inflammasome activation; however, detailed mechanism linking to remains unclear. In this study, we showed mediates stimuli-induced processing procaspase-1 consequent...

Oxidative stress is a major factor in retinal pigment epithelium (RPE) cells injury that contributes to age-related macular degeneration (AMD). NaIO3 an oxidative toxic agent and its selective RPE cell damage makes it as reproducible model of AMD. Although inducer, the roles ROS NaIO3-elicited signaling pathways viability have not been elucidated, effect on autophagy remains elusive. In human ARPE-19 cells, we used Annexin V/PI staining determine viability, immunoblotting protein expression...

Diabetic retinopathy (DR) is a major cause of blindness in adult, and the accumulation advanced glycation end products (AGEs) pathologic event DR. Methylglyoxal (MGO), highly reactive dicarbonyl compound, precursor AGEs. Although therapeutic potential metformin for disorders has recently been elucidated, possibly through AMPK activation, it remains unknown how directly affects MGO-induced stress response retinal pigment epithelial cells. Therefore, this study, we compared effects activator...

Toll-like receptors (TLRs) are a major family of pattern recognition receptors, and they play crucial role in innate immune responses. Activation TLR4 signaling at the plasma membrane by its ligand lipopolysaccharide (LPS) stimulates proinflammatory pathway dependent on E3 ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated 6) kinase TAK1 (transforming growth β-activated 1), whereas endosomes production type I interferons (IFNs) through that depends TRAF3 TBK1 (TANK-binding...

P2X7 is ubiquitously expressed in myeloid cells and regulates the pathophysiology of inflammatory diseases. Since mitochondrial function microglia highly associated with microglial functions controlling neuronal plasticity brain homeostasis, we interested to explore roles lysosomal as well mitophagy microglia.P2X7-/- bone marrow-derived macrophages (BMDM), primary BV-2 immortalized were used detect particular protein expression by immunoblotting. Mitochondrial reactive oxygen species...

IL-17 has an important role in the immunopathogenesis of autoimmune diseases, and spleen tyrosine kinase (Syk) been implicated as a critical molecule signaling pathways various immunoreceptors. Chemokine (C-C motif) ligand 20 (CCL20) interacts with chemokine receptor 6 to recruit IL-17-producing cells into skin promote progression psoriasis. Herein we investigate how Syk regulates affect CCL20 expression primary human epidermal keratinocytes. We found that can induce activate TAK, IKK,...

Abstract Poly(ADP-ribose) polymerase-1 (PARP-1) plays an essential role in DNA repair by catalyzing the polymerization of ADP-ribose unit to target proteins. Several studies have shown that PARP-1 can regulate inflammatory responses various disease models. The intracellular Nod-like receptor NLRP3 has emerged as most crucial innate immune because its broad specificity mediating response pathogen invasion and danger signals associated with cellular damage. In our study, we found...

Abstract Background Although stimulating autophagy caused by UV has been widely demonstrated in skin cells to exert cell protection, it remains unknown the cellular events UVA-treated retinal pigment epithelial (RPE) cells. Methods Human ARPE-19 were used measure viability, mitochondrial reactive oxygen species (ROS), membrane potential (MMP), mass and lysosomal flow cytometry. Mitochondrial consumption rate (OCR) was recorded using Seahorse XF flux analyzer. Confocal microscopic images...

NOD2 of the NLRs and TLR4 TLRs are major pattern-recognition receptors, which sense different microbial pathogens have important roles in innate immunity. Herein, we investigated TLR4-mediated signalling gene regulation RAW264.7 macrophages. We found that MDP (a ligand) increased LPS-induced expressions TNF-α, IL-1β, IL-6, iNOS COX-2. did not affect activation MAPKs or IKK, while it potentiated NF-κB activation. Meanwhile mRNA expression, upregulated upon treatment is a positive regulator...

Transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is a key regulator of signal cascades TNF-α receptor and TLR4, can induce NF-κB activation for preventing cell apoptosis eliciting inflammation response. TAK1 inhibitor (TAKI) decrease the viability murine bone marrow-derived macrophages (BMDM), RAW264.7 BV-2 cells, but not dermal microvascular endothelial normal human epidermal keratinocytes, THP-1 monocytes, retinal pigment epithelial microglia CHME3 some cancer lines (CL1.0,...

Spleen tyrosine kinase (Syk), a nonreceptor kinase, was initially identified as crucial regulator in proximal immunoreceptor signaling. Additional studies have revealed its pleiotropic roles, and drugs targeting Syk are under development for inflammatory diseases. expression the skin has been detected, but functions still unknown. Here, we found that phosphorylation primary human keratinocytes decreased gradually along with terminal differentiation. Human specimens showed similar vivo...

Abstract Decoy receptor 3 (DcR3) is a soluble for Fas ligand, LIGHT and TL1A, but it also exerts effector functions. Previously, we found that DcR3 upregulated in the serum lesional skin of patients with psoriasis by EGFR activation proliferating primary human epidermal keratinocytes. However, functional role intracellular keratinocyte differentiation still incompletely defined. Herein, cultured keratinocytes were differentiated phorbol 12-myristate 13-acetate (PMA) treatment, calcium...

In response to treatment with phorbol-12-myristate-13-acetate (PMA), the half-population of erythromyeloblast D2 cells, a cytokine-independent variant TF-1 displayed adhesion and differentiated into monocyte/macrophage-like morphology, while other remained in suspension underwent apoptosis. Expression cell cycle inhibitor p21(Cip1/Waf1) was induced after PMA adherent cells but not proapoptotic cells. We investigated mechanism responsible for impairment induction PMA-induced demonstrated that...

Gfi-1B (growth factor independence-1B) gene is an erythroid-specific transcription factor, whose expression plays essential role in erythropoiesis. Our laboratory has previously defined the human promoter region and shown that GATA-1 mediates transcription. By further investigating regulation of promoter, here we report (i) negatively regulated by its own product, (ii) GATA-1, instead Gfi-1B, binds directly to Gfi-1-like sites (iii) suppresses GATA-1-mediated stimulation through their...

Resveratrol, an anti-inflammatory agent, can inhibit pro-inflammatory mediators by activating Sirt1, which is a class III histone deacetylase. However, whether resveratrol regulate inhibitory or molecules has been less studied. FcγRIIB, receptor for IgG, essential of B cells blocking B-cell receptor-mediated activation and directly inducing apoptosis cells. Because mice deficient in either Sirt1 FcγRIIB develop lupus-like diseases, we investigated alleviate lupus through FcγRIIB. We found...

Calcium/calmodulin-dependent serine protein kinase (CASK) is a scaffold and plays critical roles in neuronal synaptic formation brain development. Previously, CASK was shown to associate with EGFR maintain the vulval cell differentiation C. elegans. In this study, we explored role of CHME3 microglial cells. We found that silencing protects cells from H2O2-induced death by attenuating PARP-1 activation, mitochondrial membrane potential loss, reactive oxygen species production, fission, but it...

Hypoxia has been shown to induce hypoxia-inducible factor-1alpha (HIF-1α) expression support many cellular changes required for tumor growth and metastasis. In addition hypoxia, nutrient deprivation is another stress condition widely existing in solid tumors due the poor blood supply. Our data showed that induces a significant HIF-1α protein potentiates responses of hypoxia CoCl2. This effect not because enhancement stability or transcription. Rather we found it through cap-independent but...

Gout is a common inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. This activates macrophages into proinflammatory state inducing NLRP3-dependent interleukin-1β (IL-1β) secretion, resulting neutrophil recruitment. Soluble decoy receptor 3 (DcR3) an immune modulator and can exert biological functions via non-decoy actions. Previously, we showed that DcR3 suppresses lipopolysaccharides (LPS)- virus-induced responses promotes M2 phenotype. In this...

Extracellular adenosine 5'-triphosphate (ATP) is a damage-associated molecular pattern and contributes to inflammation associated diseases including cancer. acidosis novel danger signal in the inflammatory sites, where it can modulate inflammation, immunity tumor growth. acidification was shown inhibit P2X7-mediated channel currents, while remains unknown how P2X7 together affect cellular responses. Here, we treated BV-2 microglial cells with ATP short period (<15 min) or sustained acidified...