Polymorphonuclear neutrophils (PMNs) form the first line of defense against invading microorganisms. We have shown previously that ATP release and autocrine purinergic signaling via P2Y2 receptors are essential for PMN activation. Here we show mitochondria provide initiates Stimulation formyl peptide increases mitochondrial membrane potential (Δψm) triggers a rapid burst from PMNs. This can be blocked by inhibitors production requires an initial receptor-induced Ca2+ signal The generated...

Abstract Shockwave treatment promotes bone healing of nonunion fractures. In this study, we investigated whether effect could be due to adenosine 5′-triphosphate (ATP) release-induced differentiation human mesenchymal stem cells (hMSCs) into osteoprogenitor cells. Cultured marrow-derived hMSCs were subjected shockwave and ATP release was assessed. Osteogenic mineralization evaluated by examining alkaline phosphatase activity, osteocalcin production, calcium nodule formation. Expression P2X7...

Neutrophils use chemotaxis to locate invading bacteria. Adenosine triphosphate (ATP) release and autocrine purinergic signaling via P2Y2 receptors at the front A2a back of cells regulate chemotaxis. Here, we examined intracellular mechanisms that control these opposing mechanisms. We found mitochondria deliver ATP stimulates in response chemotactic cues, promote mTOR signaling, which augments mitochondrial activity near cells. Blocking with rapamycin or PP242 production (e.g., CCCP) reduced...

Inflammation is an essential component for glial scar formation. However, the upstream mediator(s) that triggers process has not been identified. Previously, we showed expression of CD36, inflammatory mediator, occurs in a subset astcotyes peri-infarct area where forms. This study investigates role CD36 astrocyte activation and formation stroke. We observed fibrillary acidic protein (GFAP) coincided control injured astrocytes brain. Furthermore, GFAP was attenuated small interfering RNA...

Abstract Although infiltration of peripheral monocytes/macrophages is implicated in stroke pathology, vivo data regarding the deployment monocytes and their mobilization to infarct area scarce. Recent literature showed that mouse exhibit two distinct populations represent pro-inflammatory (Ly-6C hi /CCR2+) anti-inflammatory low /CCR2-) subsets spleen a major source for monocyte upon injury. By reducing post-ischemic infection with antibacterial moxifloxacin (MFX) treatment, present study...

Our previous work has shown that polymorphonuclear neutrophils (PMNs) require cellular adenosine triphosphate (ATP) release and autocrine purinergic signaling for their activation. Here we studied in a mouse model of cecal ligation puncture (CLP) whether sepsis affects this process thereby alters PMN responses after sepsis. Using high-performance liquid chromatography, found plasma ATP, diphosphate (ADP), monophosphate (AMP) concentrations increased up to 6-fold during the first 8 h CLP,...

Background/Aims: Glucagon-like peptide-1 (GLP-1)-based drugs are being used to achieve better glucose control in patients with type 2 diabetes, and GLP-1 mimetics such as liraglutide have shown therapeutic potential preventing diabetes-related microvascular macrovascular complications well comorbidities neurodegenerative disorders. In the present study, we investigated effects of on primary rat cortical astrocytes treated advanced glycation end-products (AGEs). Methods: Gene protein...

Stroke is the world's leading cause of physiological disability, but there are currently no available agents that can be delivered early after stroke to enhance recovery. Daidzein, a soy isoflavone, clinically approved agent has neuroprotective effect in vitro , and it promotes axon growth an animal model optic nerve crush. The current study investigates efficacy daidzein on neuroprotection functional recovery relevant mouse In light fact cholesterols essential lipid substrates...

Hyperlipidemia exacerbates ischemic stroke outcome and increases CD36 expression in the postischemic brain as well peripheral monocytes/macrophages. By exchanging bone marrow-derived cells between CD36-expressing CD36-deficient mice, this study investigates contribution of comparison with that to pathology hyperlipidemia.Following marrow transplantation, mice were fed a high-fat diet for 11 weeks then subjected stroke. Stroke outcome, CD36, monocyte chemoattractant protein-1 (MCP-1), CCR2,...

T cell suppression in sepsis is a well-known phenomenon; however, the underlying mechanisms are not fully understood. Previous studies have shown that stimulation up-regulates mitochondrial adenosine triphosphate (ATP) production to fuel purinergic signaling necessary for adequate responses. Here we show basal ATP production, release, and of P2X1 receptors represent standby mechanism antigen recognition. Inhibition this process impairs vigilance ability cells trigger activation, up-regulate...

Sepsis remains an unresolved clinical problem. Therapeutic strategies focusing on inhibition of neutrophils (polymorphonuclear neutrophils) have failed, which indicates that a more detailed understanding the underlying pathophysiology sepsis is required. Polymorphonuclear neutrophil activation and chemotaxis require cellular adenosine triphosphate release via pannexin-1 channels fuel autocrine feedback purinergic receptors. In current study, we examined roles endogenous systemic...

Increasing evidence suggests that chronic inflammation plays an important role in the pathogenesis of age-related macular degeneration (AMD); however, precise pathogenic stressors and sensors, their impact on disease progression remain unclear. Several studies have demonstrated type I interferon (IFN) response is activated retinal pigment epithelium (RPE) AMD patients. Previously, we human RPE cells can initiate RNA-mediated IFN responses through RIG-I, yet are unable to directly sense...

CD36, a member of the class B scavenger receptor, is high-affinity receptor for oxidatively modified low-density lipoprotein (oxLDL). Extensive evidence points to significant role CD36 in atherosclerosis and suggests that could be potential target treatment atherosclerosis. Here, extracellular domain human (Gly(30)-Asn(439)) was expressed Escherichia coli as His(6)-tagged soluble (sCD36), which bind oxLDL specifically effectively inhibit uptake by murine macrophage RAW 264.7 cells. An...

Recently, we have reported filaggrin mutations (FLG) of atopic dermatitis in southern China. However, there been few detailed reports FLG patients with AD northern China by now.The present aim was to establish the mutation spectrum gene China.A total 339 cases met Hanifin and Rajka diagnostic criteria were recruited. A comprehensive sequencing entire coding region these conducted. All detected null screened a cohort 301 normal controls.Seven novel (478insA, Q1070X, 4026delT, Q1712X, Q2397X,...

Age-related macular degeneration (AMD), a degenerative disease of the outer retina, is leading cause blindness among elderly. A hallmark geographic atrophy (GA), an advanced type nonneovascular AMD (dry AMD), photoreceptor and retinal pigment epithelium (RPE) cell death. Currently, there are no FDA-approved therapies for GA due to lack understanding disease-causing mechanisms. Increasing evidence suggests that chronic inflammation plays predominant role in pathogenesis dry AMD. Dead or...

Galanin (Gal), a bioactive neuropeptide, is widely distributed throughout the central nervous system and has diverse modulatory effects. To understand effect of this training‐stimulatory peptide on insulin sensitivity, its antagonist M35 was injected into cerebral ventricle in type 2 diabetic rats. A treadmill running rats used to stimulate circulating Gal secretion mRNA expression. The results showed that significantly decreased glucose infusion rates euglycemic–hyperinsulinemic clamp tests...

The activation of immune cells must be tightly regulated to allow an effective defence while limiting collateral damage host tissues. Cellular ATP release and autocrine stimulation purinergic receptors are recognized as critical regulators cell activation. However, the study signalling has been hampered by short half-life released its breakdown products well lack real-time imaging methods spatiotemporal dynamics release.To overcome these limitations, we optimized that monitoring with...