iNOS Polyclonal Antibody
- Known as:
- iNOS Polyclonal Antibody
- Catalog number:
- A-0475-200
- Product Quantity:
- 200
- Category:
- -
- Supplier:
- EpigenTek
- Gene target:
- iNOS Polyclonal Antibody
Related genes to: iNOS Polyclonal Antibody
- Gene:
- NOS2 NIH gene
- Name:
- nitric oxide synthase 2
- Previous symbol:
- NOS2A
- Synonyms:
- iNOS, NOS, HEP-NOS
- Chromosome:
- 17q11.2
- Locus Type:
- gene with protein product
- Date approved:
- 1993-06-15
- Date modifiied:
- 2015-12-04
Related products to: iNOS Polyclonal Antibody
Related articles to: iNOS Polyclonal Antibody
- Nitric oxide synthase 2 (NOS2) and cyclooxygenase 2 (COX2) lie at a critical intersection between inflammation, metabolism, and oncogenic signaling, where they cooperatively promote and establish a Nitric Oxide (NO)-driven Warburg phenotype in advanced cancers. Early work in macrophages established NOS2-derived NO as both a signaling molecule and metabolic stressor that inhibits oxidative phosphorylation (OXPHOS) by targeting iron-sulfur enzymes and respiratory complexes, forcing neighboring cells to rewire metabolism. In human tumors, sustained NOS2 expression in cancer cells and tumor-associated macrophages (TAMs) enforces a Warburg-like state characterized by high glycolytic flux, glutamine dependence, and enhanced NADPH production, supporting proliferation, biosynthesis, and resistance to oxidative stress. At nitrosative-signaling concentrations (≈100-500 nM), NO breaks carbon entry into the TCA cycle at aconitase and pyruvate dehydrogenase, progressively disables dehydrogenase complexes containing dihydrolipoamide dehydrogenase (DLD) and electron-transport complexes (ETCs), and activates hypoxia-inducible factor 1-alpha (HIF-1), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), extracellular signal-regulated kinase (ERK)/pyruvate kinase M2 (PKM2)/c-Myc signaling axis, nuclear factor erythroid 2-related factor 2 (Nrf2), and transforming growth factor Beta (TGF-β)/SMAD pathways. These biochemical and signaling effects convert transient glycolytic adaptation into chemically enforced dependency, further stabilized by metabolite-driven inhibition of ten-eleven translocation (TET) and Jumonji demethylases, creating an "epigenetic lock" that maintains oncogenic transcriptional programs. NOS2 and COX2 form a reciprocal feed-forward circuit in which NO, prostaglandin E2 (PGE), interleukin (IL)-6, and IL-8 reinforce one another, driving tumor-promoting inflammation, immunosuppression, angiogenesis, and metastasis while depleting nutrients and acidifying the tumor interstitial fluid. Spatially, NOS2/COX2 niches at the tumor-stroma interface and within immune deserts generate gradients of NO, PGE, oxygen, and metabolites that partition tumors into microdomains with distinct metabolic states, immune composition, and therapeutic vulnerabilities. Integrating these insights with Hanahan's updated hallmarks of cancer, we propose that NOS2-derived NO functions as a node synchronizing deregulated energetics, inflammation, immune evasion, plasticity, and therapy resistance within the tumor microenvironment (TME). Targeting the NOS2-COX2 axis and its downstream NO-iron-epigenetic circuitry may therefore disrupt multiple hallmarks and reveal combinatorial strategies to exploit NO-induced metabolic liabilities in cancer. - Source: PubMed
Publication date: 2026/06/02
Coutinho Leandro LPalmieri Erika MRidnour Lisa ACheng Robert Y SHeinz William FAnderson Stephen KBilliar Timothy RChang JennyLockett Stephen JRangel M CristinaThomas Douglas DMcVicar Daniel WWink David A - is a leading cause of pneumonia and bacteremia and is especially dangerous in healthcare settings. Despite massive clinical significance, the mechanisms used by macrophages to kill are not well defined. Macrophages are critical for controlling as mice lacking monocyte-derived or alveolar macrophages have higher bacterial tissue burdens and mortality. Two prominent mechanisms used by macrophages to kill bacteria are the production of reactive oxygen species (ROS) via the NADPH oxidase NOX2 and reactive nitrogen species (RNS) via the inducible nitric oxide synthase iNOS. Previously, we found that uses similar genetic factors to survive during bacteremia and within macrophages. The ability of these factors to enhance intracellular fitness was significantly correlated with resistance against RNS, not ROS. Here, we aimed to define whether macrophage ROS and RNS contribute to intracellular clearance. Using wild-type, , and cells, we measured survival within macrophages lacking such defenses. NOX2 was dispensable for clearance, and ROS was undetectable in infected macrophages. We confirmed that ROS was undetectable within alveolar-like macrophages, indicating a conserved ROS evasion phenotype across macrophage subsets. Instead, iNOS significantly contributed to macrophage clearance of and enhanced cytokine production. iNOS likely enhances clearance through coordination of immunity and RNS. Activation of pathways upstream of iNOS may be the most relevant to supporting effective macrophage control of . This study defines unexpected differential roles for ROS and RNS in macrophage clearance of . - Source: PubMed
Publication date: 2026/05/18
Wilcox Alexis EAndres Catherine JMadigan Elizabeth HOlive Andrew JHolmes Caitlyn L - Allergic rhinitis (AR) is driven by Th1/Th2 imbalance, with macrophages as key mediators. Vitamin D (VitD) deficiency is associated with AR; however, how VitD regulates macrophage-related molecules remains unclear. - Source: PubMed
Publication date: 2026/06/02
Huang YajingShi DingyiZhang MengniHe JiaPeng Shunlin - Clostridioides difficile infection (CDI) remains a leading cause of healthcare-associated diarrhea and is characterized by high recurrence rates and inadequate predictive tools despite available therapeutic options. Current toxin- or nucleic acid-based assays do not fully capture host inflammatory dynamics, highlighting the need for mechanistically informed host-response studies that may complement existing microbiological approaches. This study aims to clarify the molecular mechanisms through which Clostridioides difficile (C. difficile) toxins toxin A (TcdA) and toxin B (TcdB) induce CDI and establish the theoretical foundation for more targeted interventions. We systematically identified core candidate genes associated with CDI using differential expression analysis of multiple datasets, weighted gene co-expression network analysis (WGCNA), and integration of TcdA/TcdB-related gene sets derived from multiple databases. We further integrated machine learning algorithms, protein-protein interaction (PPI) network analysis, and immune infiltration analysis to investigate the relationships between TcdA/TcdB-associated host responses and immune microenvironment remodeling, defined here as inferred changes in immune-cell composition. We identified 66 candidate genes located at the intersection of CDI-associated differential expression, WGCNA-derived genes, and TcdA/TcdB-related gene sets. Machine learning algorithms further narrowed these to nine core genes: Areg, Ptgs2, Cd40, Tlr7, Aif1, Cxcl10, Il6, Cybb, and Nos2. These genes occupy key positions within inflammatory and immune-related molecular networks associated with CDI. In addition, immune infiltration analysis suggested that dysregulation of the host immune microenvironment contributes substantially to disease progression. TcdA and TcdB may contribute to the onset and progression of CDI through host transcriptional and immune programs associated with specific inflammatory signaling pathways. The nine core genes identified through machine learning, together with immune infiltration and functional enrichment analyses, support the relevance of TcdA/TcdB-associated host-response networks in CDI. These findings provide a useful foundation for future mechanistic and experimental studies aimed at clarifying the molecular basis of TcdA/TcdB-associated CDI. - Source: PubMed
Publication date: 2026/06/03
Zhao WenhuaLi HuiHu MaolingBu Tiansheng - Major depression (MD) treatments have limited efficacy and target few mechanisms, highlighting the need for innovative drug discovery. Drugs targeting genetically supported proteins are 2.6 times more likely to succeed in drug development. Here, we use genetic methods to identify and prioritise MD drug targets, leveraging genome-wide association study (GWAS) summary statistics from >525,000 MD cases. We derived exposure data from 10 datasets measuring protein quantitative trait loci (pQTLs) and gene expression levels (eQTLs) in blood, cerebrospinal fluid, and brain tissues. We performed cis-Mendelian randomisation (MR) on 3469 druggable targets (genes encoding proteins targeted by existing compounds or experimentally predicted to be druggable). To strengthen causal inference, we implemented robust MR estimators, colocalisation, external replication, and assessed directional consistency across tissues. We integrated cis-MR effect directions with drug mechanisms and clinical annotations to infer potential therapeutic effects. Validation analyses showed that 82% of drugs approved for depression/anxiety had ≥1 significant MR target, compared to 51% for compounds in clinical trials. For repurposing, we prioritised 54 targets of compounds developed for other conditions with estimated beneficial effects on MD (e.g., an inhibitor for a risk-increasing target). Ten high-priority targets of brain-penetrating compounds included ACE and NISCH (cardiovascular drugs), NDUFA2, NDUFB6, and NDUFS1 (metformin), CDK4, NTRK3, and MET (oncology inhibitors), and GLS and NOS2 (enzyme inhibitors). We found genetic evidence for established and novel MD targets across the drug development pipeline. Novel targets point to mechanisms beyond monoaminergic systems, most with approved drugs for other conditions, offering immediate repurposing opportunities. - Source: PubMed
Publication date: 2026/06/02
Ter Kuile Abigail RFinan ChrisChopade Sandeshvan Vugt MarionHukerikar NikitaBarral SerenaStringaris ArgyrisSchmidt Amand FKuchenbaecker KarolinePingault Jean-Baptiste