Regulatory T (Treg) cells play a vital role in maintaining the immunosuppressive tumor microenvironment. Lactate is crucial metabolite cancer and related to prognosis, metastasis, overall survival. In this study, we focus on effects of lactate Treg cells. vitro, improves cell stability function, whereas degradation reduces induction, increases antitumor immunity, decreases growth mice. Mechanistically, modulates generation through lactylation Lys72 MOESIN, which MOESIN interaction with...

Hepatocellular cell death and macrophage proinflammatory activation contribute to the pathology of various liver diseases, during which XBP1 plays an important role. However, function mechanism in thioacetamide (TAA)-induced acute injury (ALI) remains unknown. Here, we investigated effects inhibition on promoting hepatocellular pyroptosis activate STING signaling ALI. While both TAA- LPS-induced ALI triggered hepatocytes, hepatocyte-specific knockout mice exhibited exacerbated with increased...

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease associated with dysregulation of metabolism and inflammation. G-protein coupled bile acid receptor 1 (TGR5) cell surface that involved in multiple metabolic pathways. However, the functions TGR5 regulating macrophage innate immune activation NASH remain unclear. Here, we found expression was decreased tissues from humans mice NASH. Compared to wild type (WT) mice, TGR5-knockout (TGR5-/-) exhibited exacerbated damage, increased...

Non-alcoholic steatohepatitis (NASH) is associated with the dysregulation of lipid metabolism and hepatic inflammation, though underlying mechanisms remain unclear. We aimed to investigate role X-box binding protein-1 (XBP1) in progression NASH.

Abstract Macrophage‐stimulator of interferon genes (STING) signaling mediated sterile inflammation has been implicated in various age‐related diseases. However, whether and how macrophage mitochondrial DNA (mtDNA) regulates STING aged macrophages remains largely unknown. We found that hypoxia‐reoxygenation (HR) induced activation by triggering the release mtDNA into cytosol. Aging promoted cytosolic leakage enhanced activation, which was abrogated upon depletion or cyclic GMP‐AMP Synthase...

Oxidative stress-mediated ferroptosis and macrophage-related inflammation play an important role in various liver diseases. Here, we explored if how hepatocyte regulates macrophage stimulator of interferon genes (STING) activation the development spontaneous damage, fibrosis, tumorigenesis.We used a transforming growth factor-beta-activated kinase 1 (TAK1) deficiency-induced model tumorigenesis to investigate its impact on STING signalling. Primary hepatocytes macrophages were for vitro...

Although aggravated liver injury has been reported in aged livers post-ischemia and reperfusion (IR), the underlying mechanism of innate immune activation macrophages is not well understood. Here, we investigated whether how Stimulator interferon genes (STING) signaling regulated macrophage proinflammatory IR injury. Mice were subjected to hepatic vivo. Macrophages isolated from IR-stressed bone marrow-derived (BMDMs) young mice used for vitro studies. Enhanced nucleotide-binding domain...

Liver-resident macrophages (Kupffer cells, KCs) and autophagy play critical roles in the pathogenesis of toxin-induced liver injury. Recent evidence indicates that can regulate macrophage M1/M2 polarization under different inflammatory conditions. Polyamines, including putrescine, spermidine, spermine (SPM), are polycations with anti-oxidative, anti-aging, cell induction properties. This study aimed to determine mechanisms by which SPM protects against thioacetamide (TAA)-induced acute...

XBP1 modulates the macrophage proinflammatory response, but its function in stimulator of interferon genes (STING) activation and liver fibrosis is unknown. X-box binding protein 1 (XBP1) has been shown to promote nucleotide-binding oligomerization domain, leucine-rich repeat pyrin domain-containing 3 (NLRP3) steatohepatitis. Herein, we aimed explore underlying mechanism regulation STING signalling subsequent NLRP3 during fibrosis.XBP1 expression was measured human fibrotic tissue samples....

Aged livers have shown aggravated liver ischemia and reperfusion (IR) injury. Timely efferocytosis of apoptotic cells is a key mechanism for avoiding excessive inflammation tissue Here, we investigated the alteration by aged macrophages its role in regulating macrophage STING (stimulator interferon genes) signaling IR young mice were subjected to partial model. Liver injury measured. Efferocytosis underlying regulatory analyzed as well. exhibited impaired with decreased MerTK (c-mer...

Background: Fatty livers are widely accepted as marginal donors for liver transplantation but more susceptible to ischemia and reperfusion (IR) injury. Increased macrophage-related inflammation plays an important role in the aggravation of fatty IR Here, we investigate precise mechanism by which endoplasmic reticulum (ER) stress activates macrophage NOD-like receptor thermal protein domain–associated 3 (NLRP3) signaling regulating mitochondrial calcium overload IR. Methods: Control- high-fat...

To assess the potential for injury to normal tissues in mice due heating systemically delivered magnetic nanoparticles an alternating field (AMF).Twenty three male nude received intravenous injections of dextran-superparamagnetic iron oxide on days 1-3. On day 6, they were exposed AMF. 7, blood, liver and spleen harvested analyzed.Iron deposits detected spleen. Mice that had a high-particle dose high AMF experienced increased mortality, elevated enzymes significant necrosis. treated with...

Abstract Although mechanisms of immune activation against liver ischemia reperfusion (IR) injury (IRI) have been studied extensively, questions regarding liver-resident macrophages, that is, Kupffer cells (KCs), remain controversial. Recent progress in the biology tissue-resident macrophages implicates homeostatic functions KCs. This study aims to dissect responses and KCs IRI. In a murine partial warm model, we analyzed versus infiltrating by FACS immunofluorescence staining. Our data...

Liver fibrosis is a common pathological process of end-stage liver diseases. However, the role microRNA (miRNA) in poorly understood. The activated hepatic stellate cells (HSCs) are major source fibrogenic and play central fibrosis. In this study, we investigated differential expression miRNAs resting transforming growth factor β1 (TGF-β1) HSCs by microarray analysis found that miR-455-3p was significantly downregulated during activation. addition, reduction correlated with mice carbon...

Abstract Although the detrimental effects of diabetes mellitus/hyperglycemia have been observed in many liver disease models, function and mechanism hyperglycemia regulating liver‐resident macrophages, Kupffer cells (KCs), thioacetamide ( TAA )‐induced injury remain largely unknown. In this study, we evaluated role NOD‐like receptor family pyrin domain‐containing 3 protein (NLRP3) inflammasome activation by inhibiting autophagy induction KC s ‐induced model. Type I diabetes/hyperglycemia was...

The plasma membrane-bound G protein-coupled bile acid receptor (TGR5) displays varied levels of expression in different tissues. TGR5-induced liver protection has been demonstrated during several diseases, except ischemia/reperfusion injury (IRI). Male adult wild-type and TGR5 knockout (KO) mice were subjected to partial warm ischemia/reperfusion. Hepatic was evaluated based on serum alanine aminotransferase aspartate aminotransferase. Liver histological inflammatory cell infiltration tissue...

Abstract Although diabetes mellitus/hyperglycemia is a risk factor for acute liver injury, the underlying mechanism remains largely unknown. Liver-resident macrophages (Kupffer cells, KCs) and oxidative stress play critical roles in pathogenesis of toxin-induced injury. Here, we evaluated role regulating KC polarization against acetaminophen (APAP)-mediated injury streptozotocin-induced hyperglycemic murine model. Compared to controls, mice exhibited significant increase intrahepatic...

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is an unmet clinical challenge due to the rapid increased occurrence but lacking approved drugs. Autophagy-related protein 16-like 1 (ATG16L1) plays important role in process of autophagy, which indispensable for proper biogenesis autophagosome, its modulating macrophage-related inflammation and metabolism during MASH has not been documented. Here, we aimed elucidate ATG16L1 progression MASH.Methods: Expression analysis...

The current standard of care for patients with locally advanced prostate cancer is a combination androgen deprivation and radiation therapy. Radiation typically given suppression when testosterone levels are at their nadir. Recent reports have shown that stimulation androgen-deprived cells leads to formation double-strand breaks (DSB). Here, we exploit this finding investigate the extent timing androgen-induced DSBs effect on tumor growth following in ionizing (IR).Androgen-induced DNA...

Liver fibrosis is an important pathologic process in injured liver tissues. A protein kinase, receptor-interacting (RIP)3, plays a crucial role mediating different diseases. However, the of RIP3 macrophages has not yet been studied. In our study, we found that expression was up-regulated tissues and humans mice with fibrosis. Absence could alleviate inflammation macrophage or neutrophil accumulation after carbon tetrachloride (CCl4) bile duct ligation (BDL) treatment. Importantly, deficiency...

The role and underlying mechanism of plasma membrane-bound G protein-coupled bile acid receptor (TGR5) in regulating macrophage innate immune activation during liver ischemia reperfusion (IR) injury remains largely unclear. Here, we demonstrated that TGR5 depletion myeloid cells aggravated with increased infiltration enhanced inflammation livers post-IR. While deficiency mobility proinflammatory M1 polarization macrophages, agonist the anti-inflammatory effect both vivo vitro. Microarray...

Liver fibrosis is a patho-physiological process which can develop into cirrhosis, and hepatic carcinoma without intervention. Our study extensively investigated the mechanisms of lncRNA NEAT1 miR-139-5p in regulating liver progression. results demonstrated that expression was increased decreased fibrotic tissues. LncRNA could sponge promoted stellate cells (HSCs) activation by directly inhibiting miR-139-5p. The co-localization with shown cytosols activated HSCs. upregulation suppress...