European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 275, P. 116576 - 116576
Published: June 7, 2024
Language: Английский
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: Oct. 26, 2023
Acute liver failure (ALF) is a severe disease caused by disruptions in the body’s immune microenvironment. In early stages of ALF, Kupffer cells (KCs) become depleted and recruit monocytes derived from bone marrow or abdomen to replace macrophages entering liver. These differentiate into mature macrophages, which are activated microenvironment polarized perform various functions. Macrophage polarization can occur two directions: pro-inflammatory M1 anti-inflammatory M2 macrophages. Controlling ratio direction ALF help reduce injury. However, damage pyroptosis should not be underestimated, as it caspase-dependent form cell death. Inhibiting has been shown effectively induced ALF. Furthermore, macrophage share common binding sites, signaling pathways, outcomes. review, we describe role pathogenesis Additionally, preliminarily explore relationship between pyroptosis, well their effects on
Language: Английский
Citations
19
International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(21), P. 15528 - 15528
Published: Oct. 24, 2023
The complex interplay between dietary factors, inflammation, and macrophage polarization is pivotal in the pathogenesis progression of chronic liver diseases (CLDs). Omega-3 fatty acids (FAs) have brought attention due to their potential modulate inflammation exert protective effects various pathological conditions. eicosapentaenoic acid (EPA) docosahexaenoic (DHA) shown promise mitigating enhancing resolution inflammatory responses. They influence M1/M2 phenotype balance, promoting a shift towards M2 anti-inflammatory phenotype. Specialized pro-resolving mediators (SPMs), such as resolvins (Rvs), protectins (PDs), maresins (MaRs), emerged potent regulators polarization. show properties, by modulating expression cytokines, facilitate phagocytosis apoptotic cells, promote tissue repair. MaR1, particular, has demonstrated significant hepatoprotective polarization, reducing oxidative stress, inhibiting key pathways NF-κB. In context CLDs, nonalcoholic disease (NAFLD) cirrhosis, omega-3s SPMs attenuating injury, regeneration, phenotypes. aim this article was analyze emerging role omega-3 FAs with special interest mechanisms underlying interactions other cell types within microenvironment, focused on CLDs development novel therapeutic strategies.
Language: Английский
Citations
18
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15
Published: Feb. 6, 2024
Macrophages play a critical role in innate immunity, with approximately 90% of the total macrophage population human body residing liver. This encompasses both resident and infiltrating macrophages. Recent studies highlight pivotal liver macrophages various aspects such as inflammation, regeneration, immune regulation. A novel pro-inflammatory programmed cell death, pyroptosis, initially identified macrophages, has garnered substantial attention since its discovery. Studies investigating pyroptosis inflammation progression have particularly centered around In diseases, plays an important driving inflammatory response, facilitating fibrotic process, promoting tumor progression. Notably, cannot be understated. review primarily focuses on diseases. Additionally, it underscores therapeutic potential inherent targeting pyroptosis.
Language: Английский
Citations
8
Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 1349 - 1364
Published: Feb. 1, 2024
Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) pro-resolution lipid mediator that promotes the resolution of inflammation protects organs from inflammation. Methods: In this study, we established an SA-AKI model using cecal ligation puncture (CLP) investigated effect mechanism MaR1. The blood kidneys were harvested 24 hours after surgery. biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, AMPK/SIRT3 signaling septic mice observed by histological staining, immunohistochemical Western blot, qPCR, ELISA TUNEL Assay. Results: MaR1 treatment alleviated mice, reflected improved pathological changes structure function. decreased levels serum creatinine (sCr) urea nitrogen (BUN) expressions KIM-1, NGAL TIMP-2, which related to injury, while inhibited inflammatory factors TNF-α, IL-1β IL-6. expression endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, pyroptosis-related Caspase-1, NLRP3, GSDMD, IL-18, also treatment. may be activation pathway, AMPK inhibitor (compound C) partially reverses MaR1's protective effects mice. Conclusion: Taken together, these findings suggest ameliorate activating providing potential new perspective for research on SA-AKI. Keywords: Maresin-1, pyroptosis, AMPK/SIRT3, stress, sepsis-associated
Language: Английский
Citations
8
Annals of Hepatology, Journal Year: 2024, Volume and Issue: 29(4), P. 101475 - 101475
Published: Feb. 6, 2024
Acute liver injury (ALI) is characterized by massive hepatocyte death with high mortality and poor prognosis. Hepatocyte pyroptosis plays a key role in the physiopathological processes of ALI, which can damage mitochondria release NLRP3 inflammasome particles, causing systemic inflammatory responses. Z-DNA Binding Protein 1 (ZBP1) sensor that induces cell death. Here, we investigated whether ZBP1 participates explored possible pathogenesis ALI. pyrotosis was induced lipopolysaccharide (LPS) nigericin (Nig), expression Zbp1 examined western blot analysis RT-qPCR. Further, transfected AML-12 (LO2 HepG2) lines siRNA. After silenced, LDH flow cytometry were used to measure death; Western RT-qPCR detect marker activation pyroptosis. We also detected mitochondrial linear rupture phosphoglycerate mutase family member 5 (PGAM5) using reactive oxygen species (ROS) DCFH-DA method. The up-regulated LPS/Nig-induced hepatocytes. Si-Zbp1 (Si-ZBP1) inhibited Moreover, silencing PGAM5 reducing ROS production. promotes hepatocellular modulating damage, facilitates extracellular ROS.
Language: Английский
Citations
6
Molecular Medicine Reports, Journal Year: 2024, Volume and Issue: 29(4)
Published: Feb. 20, 2024
Acetaminophen (APAP) overdose is the primary cause of drug‑induced acute liver failure in numerous Western countries. NLR family pyrin domain containing 3 (NLRP3) inflammasome activation serves a pivotal role pathogenesis various forms injury. However, cellular source for NLRP3 induction and its involvement during APAP‑induced hepatotoxicity have not been thoroughly investigated. In present study, hematoxylin eosin staining was performed to assess histopathological changes tissue. Immunohistochemistry staining(NLRP3, Caspase‑1, IL‑1β, GSDMD Caspase‑3), western blotting (NLRP3, Caspase‑3) RT‑qPCR Caspase‑1 IL‑1β) were expression NLRP3/GSDMD signaling pathway. TUNEL apoptosis The serum levels inflammatory factors (IL‑6, IL‑18, IL‑1β TNF‑α) assessed using ELISA inflammation tissue immunohistochemistry (Ly6G CD68) (TNF‑α, Il‑6, Mcp‑1, Cxcl‑1, Cxcl‑2). A Cell Counting Kit‑8 cell viability apoptosis. Protein gene analyzed by (PCNA, CCND1) (CyclinA2, CyclinD1 CyclinE1). Through investigation an injury model (AILI), study demonstrated that APAP induced cleavage gasdermin D (GSDMD) hepatocytes, both in vivo vitro. Additionally, mice with hepatocyte‑specific knockout Nlrp3 exhibited reduced lower mortality following intervention, accompanied decreased infiltration cells attenuated response. Furthermore, pharmacological blockade MCC950 or disulfiram significantly ameliorated hepatocyte death. Notably, deficiency promoted recovery enhancing proliferation. Collectively, inhibition protects against reducing pyroptosis suggests targeting may hold therapeutic potential treating AILI.
Language: Английский
Citations
6
International Immunopharmacology, Journal Year: 2024, Volume and Issue: 135, P. 112277 - 112277
Published: May 23, 2024
Language: Английский
Citations
6
Genes & Diseases, Journal Year: 2022, Volume and Issue: 10(4), P. 1552 - 1563
Published: June 20, 2022
Inflammatory bowel disease (IBD) is a chronic relapsing gastrointestinal disorder, while the treatment effect not satisfactory. Immune responsive gene 1 (IRG1) highly expressed in macrophage response to inflammatory and catalyzes production of itaconate. Studies have reported that IRG1/itaconate has significant antioxidant effect. This study aimed investigate mechanism on dextran sulfate sodium (DSS)-induced colitis vivo vitro. In experiments, we found exerted protective effects against acute by increasing mice weight, length colon, reducing activity index colonic inflammation. Meanwhile, IRG1 deletion aggravated macrophages/CD4+/CD8+ T-cell accumulation, increased release interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-6, activation nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, gasdermin D (GSDMD) mediated pyroptosis. Four-octyl itaconate (4-OI), derivative itaconate, attenuated these changes, therefore relieved DSS-induced colitis. vitro experiment, 4-OI inhibited reactive oxygen species production, thereby inhibiting MAPK/NF-κB pathway RAW264.7 murine bone-marrow-derived macrophages. Simultaneously, caspase1/GSDMD-mediated pyroptosis reduce cytokines. Finally, anti-TNF-α agent reduced severity E (GSDME)-mediated vivo. our revealed caspase3/GSDME-mediated induced TNF-α Taken together, role GSDMD/GSDME-mediated pyroptosis, which could be promising candidate for IBD therapy.
Language: Английский
Citations
26
Inflammopharmacology, Journal Year: 2023, Volume and Issue: 32(1), P. 419 - 432
Published: July 20, 2023
Language: Английский
Citations
16
Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)
Published: Dec. 2, 2023
Metabolic states greatly influence functioning and differentiation of immune cells. Regulating the metabolism cells can effectively modulate host response. Itaconate, an intermediate metabolite derived from tricarboxylic acid (TCA) cycle cells, is produced through decarboxylation cis-aconitate by decarboxylase in mitochondria. The gene encoding known as response 1 (IRG1). In to external proinflammatory stimulation, macrophages exhibit high IRG1 expression. IRG1/itaconate inhibits succinate dehydrogenase activity, thus influencing metabolic status macrophages. Therefore, itaconate serves a link between macrophage metabolism, oxidative stress, response, ultimately regulating function. Studies have demonstrated that acts on various signaling pathways, including Keap1-nuclear factor E2-related 2-ARE ATF3-IκBζ axis, stimulator interferon genes (STING) pathway exert antiinflammatory antioxidant effects. Furthermore, several studies reported affects cancer occurrence development diverse pathways. this paper, we provide comprehensive review role its derivatives regulation functions. By furthering our understanding itaconate, intend shed light potential for treating inflammatory diseases offer new insights field.
Language: Английский
Citations
15