Only in Titles

Search results for: arginase

paperclip

#36473034   2022/12/04 To Up

Dimethyl Sulfoxide Induces Hemolysis and Pulmonary Hypertension.

Vascular and lung injury are well established complications associated with hemolytic disorders, and hemolysis associated pulmonary hypertension (PH) has emerged as the most serious complication of sickle cell disease. The causal relationship between intravascular hemolysis and the development of PH is still under investigation. Previously we have shown that repetitive administration of hemolyzed autologous blood causes PH in rats. Dimethyl sulfoxide (DMSO), a widely used solvent and anti-inflammatory agent, induces hemolysis in vivo. We hypothesized that repetitive administration of DMSO would induce PH in rats. We also examined hemolysis-induced release of adenosine deaminase (ADA) and arginase from red blood cells, which may amplify hemolysis-mediated vascular injury. Acute administration of DMSO (1.5ml/30 min into the right atrium) induced intravascular hemolysis and pulmonary vasoconstriction. DMSO-induced increase in right ventricular peak systolic pressure (RVPSP) was associated with increased release of ADA. Notably, the acute increase in RVPSP was attenuated by administration of an adenosine A2A receptor agonist or by pretreatment of animals with ADA inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). Repetitive administration of DMSO for 10 days produced anemia, hemoglobinuria, hemoglobinemia, splenomegaly, and development of PH. Histopathological analysis revealed pulmonary vascular remodeling. The presented data describe a new model of hemolysis induced PH, suggesting that hemolysis is mechanistically related to pulmonary hypertension, and pointing to a potential pathogenic role that adenosine deaminase and accelerated adenosine metabolism may play in hemolysis associated pulmonary hypertension.
Stevan P Tofovic, Victor P Bilan, Olga Rafikova, Frank Schneider, Enrico M Novelli, Edwin K Jackson

1326 related Products with: Dimethyl Sulfoxide Induces Hemolysis and Pulmonary Hypertension.

2x5L 1L500 MG 500 G100 mg10 mg1 mg1 mg 25 G25 mg1 g 25 G

Related Pathways

paperclip

#36471170   2022/12/05 To Up

Ammonia detoxification promotes CD8 T cell memory development by urea and citrulline cycles.

Amino acid metabolism is essential for cell survival, while the byproduct ammonia is toxic and can injure cellular longevity. Here we show that CD8 memory T (T) cells mobilize the carbamoyl phosphate (CP) metabolic pathway to clear ammonia, thus promoting memory development. CD8 T cells use β-hydroxybutyrylation to upregulate CP synthetase 1 and trigger the CP metabolic cascade to form arginine in the cytosol. This cytosolic arginine is then translocated into the mitochondria where it is split by arginase 2 to urea and ornithine. Cytosolic arginine is also converted to nitric oxide and citrulline by nitric oxide synthases. Thus, both the urea and citrulline cycles are employed by CD8 T cells to clear ammonia and enable memory development. This ammonia clearance machinery might be targeted to improve T cell-based cancer immunotherapies.
Ke Tang, Huafeng Zhang, Jinghui Deng, Dianheng Wang, Shichuan Liu, Shuya Lu, Qingfa Cui, Chen Chen, Jincheng Liu, Zhuoshun Yang, Yonggang Li, Jie Chen, Jiadi Lv, Jingwei Ma, Bo Huang

2498 related Products with: Ammonia detoxification promotes CD8 T cell memory development by urea and citrulline cycles.

132/kit250.5 mg100 μg0.1ml (1mg/ml)

Related Pathways

paperclip

#36464273   2022/12/05 To Up

Loss of AKAP12 aggravates rheumatoid arthritis-like symptoms and cardiac damage in collagen-induced arthritis mice.

A-kinase anchoring protein 12 (AKAP12) has been identified as an anti-inflammatory and anti-fibrotic regulator in chronic inflammation and cardiovascular disease. However, the potential of AKAP12 in autoimmune disorders, rheumatoid arthritis (RA) and associated cardiac complications remains elusive. Here, a murine model of collagen-induced arthritis (CIA) was successfully induced, followed by adenovirus-mediated AKAP12 short hairpin RNA (shRNA) treatment. AKAP12 silenced mice displayed elevated clinical arthritis scores and significant ankle joint swelling. AKAP12 loss in CIA mice increased inflammatory cell infiltration and cartilage erosion, increased the levels of anti-IIC IgG and inflammatory cytokines IL-1β, IL-6, TNF-α in serum, and upregulated the expression of cartilage-degrading enzymes MMP-1, MMP-3, MMP-13 in synovium, but reduced IL-10. The number of M1 macrophages and the expression of the markers (CCR7, IL-6, TNF-α and iNOS) was enhanced in synovial tissues, while M2 polarized macrophages and the makers (IL-10 and arginase-1) were reduced in response to AKAP12 loss. Moreover, low expression of AKAP12 was detected in the hearts of CIA mice. Loss of AKAP12 results in increased cardiac inflammation and fibrosis. This work suggests that AKAP12 loss aggravates joint inflammation likely through the promotion of M1 macrophage polarization and exacerbates inflammation-caused cardiac fibrosis.
Yanhui Ni, Jingjing Cao, Jing Yuan, Xiaoran Ning

2880 related Products with: Loss of AKAP12 aggravates rheumatoid arthritis-like symptoms and cardiac damage in collagen-induced arthritis mice.

96 assays100 μg1 mg24 tests100 ul 100ul100ug50 ul100ug50 ul400 ug96 samples

Related Pathways

paperclip

#36462310   2022/11/30 To Up

Elafibranor modulates ileal macrophage polarization to restore intestinal integrity in NASH: Potential crosstalk between ileal IL-10/STAT3 and hepatic TLR4/NF-κB axes.

Experimental and clinical evidence implicate disrupted gut barrier integrity in provoking innate immune responses, specifically macrophages, towards the progression of non-alcoholic steatohepatitis (NASH). Peroxisome proliferator-activated receptors (PPARs), a subset of the nuclear receptor superfamily, act to fine-tune several metabolic and inflammatory processes implicated in NASH. As such, the current study was carried out to decipher the potential role of dual PPAR α/δ activation using elafibranor (ELA) on ileal macrophage polarization (MP) and its likely impact on the liver in a NASH setting. To achieve this aim, an in vitro NASH model using fat-laden HepG2 cells was first used to validate the impact of ELA on hepatic fat accumulation. Afterwards, ELA was used in a combined model of dietary NASH and chronic colitis analogous to the clinical presentation of NASH parallel with intestinal barrier dysfunction. ELA mitigated fat accumulation in vitro as evidenced by Oil Red-O staining and curbed triglyceride levels. Additionally, ELA restored the expression of tight junctional proteins, claudin-1 and occludin, along with decreasing intestinal permeability and inflammation skewing ileal macrophages towards the M2 phenotype, as indicated by boosted arginase-1 (Arg1) and curtailed inducible nitric oxide synthase (iNOS) expression levels. These changes were aligned with a modulation in hepatic toll-like receptor-4 (TLR4)/nuclear factor kappa B (NF-κB) along with ileal interleukin-10 (IL-10)/signal transducer and activator of transcription-3 (STAT3) axes. Overall, the present findings suggest that the dual PPAR α/δ agonist, ELA, may drive MP in the ileum towards the M2 phenotype improving intestinal integrity towards alleviating NASH.
Andrew N Hakeem, Mohamed M Kamal, Rasha A Tawfiq, Basma A Abdelrahman, Olfat A Hammam, Mohamed M Elmazar, Aiman S El-Khatib, Yasmeen M Attia

1133 related Products with: Elafibranor modulates ileal macrophage polarization to restore intestinal integrity in NASH: Potential crosstalk between ileal IL-10/STAT3 and hepatic TLR4/NF-κB axes.

96 wells (1 kit)100ug Lyophilized5ug1 Set96 assays100ug25 1 Set5 mg1mg100ug

Related Pathways

paperclip

#36461608   2022/11/09 To Up

A modulatory effect of L-arginine supplementation on anticancer effects of chemoimmunotherapy in colon cancer-bearing aged mice.

Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are increased in cancer-bearing aged hosts. Arginase-I in MDSCs degrades L-arginine, an amino acid required for T cell activation and proliferation. In this study, we compared the therapeutic efficacy of 5-fluorouracil (5-FU)/oxaliplatin (L-OHP) and cyclophosphamide (CP) between young and aged colon cancer-bearing mice. Therapy with 5-FU/L-OHP and CP significantly suppressed the in vivo growth of CT26 and MC38 colon carcinomas in syngeneic young mice, whereas this effect was attenuated in aged mice. L-arginine monotherapy showed no effect in aged mice. However, additional therapy with anti-programmed cell death (PD)-1 antibody and L-arginine supplementation boosted the effect of chemoimmunotherapy in aged mice, and some mice were cured. During all combination therapy, tumor-specific cytotoxic T lymphocytes (CTLs) were generated from mice with non-progressing tumor, but not from those with progressing tumor. Plasma L-arginine levels were lower in aged than young mice, and chemotherapy tended to decrease the plasma L-arginine levels in aged mice. Compared to young mice, CT26-bearing aged mice decreased arginase activity, arginase-I expression, and the proportion of monocytic MDSCs in tumor tissues, whereas contrasting results were observed in MC38-bearing aged mice. Importantly, the induction of tumor-specific CTLs was impaired at lower doses of L-arginine in vitro, and the infiltration of CTLs into CT26 tissues after chemoimmunotherapy was promoted by L-arginine administration in vivo. These results indicate that chemoimmunotherapy was less effective in cancer-bearing aged mice, but that L-arginine supplementation can modulate its therapeutic efficacy via its effect on tumor-specific CTLs.
Kazunari Ishitobi, Hitoshi Kotani, Yuichi Iida, Takahito Taniura, Yoshitomo Notsu, Yoshitsugu Tajima, Mamoru Harada

1614 related Products with: A modulatory effect of L-arginine supplementation on anticancer effects of chemoimmunotherapy in colon cancer-bearing aged mice.



Related Pathways

paperclip

#36452219   2022/11/14 To Up

Novel recombinant protein flagellin A N/C attenuates experimental autoimmune encephalomyelitis by suppressing the ROS/NF-κB/NLRP3 signaling pathway.

Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease characterized by demyelination and neurodegeneration, for which traditional treatment offers limited relief. Microglial/macrophage modulation plays a critical role in the pathogenesis of MS. Oxygen free radical accumulation can induce axonal and nerve cell damage, and further promote MS development. We created a new recombinant protein based on flagellin from named flagellin A with linked - and -terminal ends (FLaAN/C), which is an independent intellectual property of our team. We previously showed that FLaAN/C might mitigate radiation-induced damage by inhibiting inflammatory responses and oxidative stress. However, whether FLaAN/C protects against MS remains unknown. Here, we investigated the anti-inflammatory effects of FLaAN/C on mice with experimental autoimmune encephalomyelitis (EAE) induced by oligodendrocyte glycoprotein peptide 35-55 (MOG35-55). The mice were injected intraperitoneally with FLaAN/C after the onset of clinical symptoms, then clinical behavior scores and changes in body weight were recorded daily. The spinal lumbar spine in model mice was enlarged and accompanied by inflammatory cell infiltration and demyelination that were reversed by FLaAN/C. FLaAN/C also induced microglia/macrophages to generate less pro-inflammatory (CD86, iNOS, and TNF-α), and more anti-inflammatory (CD206, IL-10, and Arginase-1) cytokines. These findings suggesting that FLaAN/C promoted microglial/macrophages polarization from the inflammatory M1 to the anti-inflammatory M2 phenotype. Moreover, FLaAN/C inhibited release of the inflammatory cytokines, TNF-α, IL-8, IL-6, IL-17, and IFN-γ. These results indicated that the anti-inflammatory effect of FLaAN/C was associated with the inhibited generation of reactive oxygen species. FLaAN/C downregulated the expression of phosphorylated NF-κB-p65 and prevented downstream NLRP3 inflammasome-mediated pyroptosis. Collectively, these results indicated that FLaAN/C prevents pyroptosis by inhibiting the ROS/NF-κB/NLRP3 signaling pathway, and promotes the microglial/macrophage M1/M2 polarization that significantly alleviated inflammation in mouse models of EAE. Our findings suggested that FLaAN/C could be a promising candidate for MS therapy.
Li Li, Shihua Deng, Mingquan Liu, Min Yang, Jin Li, Teng Liu, Ting Zhang, Yangyang Zhao, Miao He, Dongming Wu, Ying Xu

1296 related Products with: Novel recombinant protein flagellin A N/C attenuates experimental autoimmune encephalomyelitis by suppressing the ROS/NF-κB/NLRP3 signaling pathway.

20221 mg201mg2050100 1mg1mg20

Related Pathways

paperclip

#36451006   2022/12/01 To Up

Autophagic reprogramming of bone marrow-derived macrophages.

Macro-autophagy is a highly conserved catabolic process among eukaryotes affecting macrophages. This work studies the genetic regulatory network involving the interplay between autophagy and macrophage polarization (activation). Autophagy-related genes (Atgs) and differentially expressed genes (DEGs) of macrophage polarization (M1-M2) were predicted, and their regulatory networks constructed. Naïve (M0) mouse bone marrow-derived monocytes were differentiated into M1 and M2a. Validation of the targets of Smad1, LC3A and LC3B, Atg16L1, Atg7, IL-6, CD68, Arg-1, and Vamp7 was performed in vitro. Immunophenotyping by flow cytometry revealed three macrophage phenotypes: M0 (IL-6 + /CD68 +), M1 (IL-6 + /CD68 + /Arg-1 +), and M2a (CD68 + /Arg-1). Confocal microscopy revealed increased autophagy in both M1 and M2a and a significant increase in the pre-autophagosomes size and number. Bafilomycin A increased the expression of CD68 and Arg-1 in all cell lineages. In conclusion, our approach predicted the protein targets mediating the interplay between autophagy and macrophage polarization. We suggest that autophagy reprograms macrophage polarization via CD68, arginase 1, Atg16L1-1, and Atg16L1-3. The current findings provide a foundation for the future use of macrophages in immunotherapy of different autoimmune disorders.
Mayada Mazher, Yomna Adel Moqidem, Mona Zidan, Ahmed A Sayed, Ahmed Abdellatif

2094 related Products with: Autophagic reprogramming of bone marrow-derived macrophages.

100ug1 ml100 ug100 100ug Lyophilized100 µg

Related Pathways

paperclip

#36445361   // To Up

Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients.

Juvenile idiopathic arthritis (JIA) is an inflammatory rheumatic disorder. Polymorphonuclear neutrophils (PMNs) are present in JIA synovial fluid (SF), but with variable frequency. SF PMNs in JIA were previously shown to display high exocytic but low phagocytic and immunoregulatory activities. To further assess whether the degree of SF neutrophilia associated with altered immune responses in JIA, we collected SF and blood from 16 adolescent JIA patients. SF and blood leukocytes were analyzed by flow cytometry. SF and plasma were used for immune mediator quantification and metabolomics. Healthy donor blood T cells were cultured in SF to evaluate its immunoregulatory activities. PMN and T cell frequencies were bimodal in JIA SF, delineating PMN high/T cell low (PMNHigh) and PMN low/T cell high (PMNLow) samples. Proinflammatory mediators were increased in SF compared with plasma across patients, and pro- and anti-inflammatory mediators were further elevated in PMNHigh SF. Compared to blood, SF PMNs showed increased exocytosis and programmed death-1/programmed death ligand-1 expression, and SF PMNs and monocytes/macrophages had increased surface-bound arginase-1. SPADE analysis revealed SF monocyte/macrophage subpopulations coexpressing programmed death-1 and programmed death ligand-1, with higher expression in PMNHigh SF. Healthy donor T cells showed reduced coreceptor expression when stimulated in PMNHigh versus PMNLow SF. However, amino acid metabolites related to the arginase-1 and IDO-1 pathways did not differ between the two groups. Hence, PMN predominance in the SF of a subset of JIA patients is associated with elevated immune mediator concentration and may alter SF monocyte/macrophage phenotype and T cell activation, without altering immunoregulatory amino acids.
Vincent D Giacalone, Alexandre Cammarata-Mouchtouris, Diego Moncada-Giraldo, Sreekala P V Shenoy, Lori A Ponder, Talia R Gergely, Susan O Kim, Joshua D Chandler, Patricia Vega-Fernandez, Cynthia K Manos, Elaine R Flanagan, Sampath Prahalad, Rabindra Tirouvanziam

1077 related Products with: Immunometabolic Analysis of Synovial Fluid from Juvenile Idiopathic Arthritis Patients.

5ml1 module100ml2 modules2 modules 15 ml 1 module1 module1 module1 module

Related Pathways

paperclip

#36440573   2022/11/28 To Up

Calcaratarin D, a labdane diterpenoid, attenuates mouse asthma via modulating alveolar macrophage function.

Alveolar macrophages (AMs) contribute to airway inflammation and remodeling in allergic asthma. Calcaratarin D (CalD), a labdane diterpenoid isolated from the rhizomes of the medicinal plant Alpinia calcarata, has recently been shown to possess anti-inflammatory properties. The present study evaluated protective effects of CalD in a house dust mite (HDM)-induced asthma mouse model.
Wupeng Liao, Hazel Y C Foo, Thi Ngoc Quy Tran, Christina L L Chai, W S Fred Wong

1399 related Products with: Calcaratarin D, a labdane diterpenoid, attenuates mouse asthma via modulating alveolar macrophage function.

100 ug/vial200.00 ug2 mL100 ug/vial0.2 mL5ug0.5 ml200.00 ug25 TESTS20 200.00 ug200.00 ug

Related Pathways

paperclip

#36439093   2022/11/09 To Up

Characterization of exosomes derived from IPEC-J2 treated with probiotic SC06 and its regulation of macrophage functions.

Probiotics can maintain or improve health by modulating the response of immune cells in the gastrointestinal tract. However, the mechanisms by which probiotics promote macrophage (Mφ) activity are poorly understood. Here, we evaluated exosomes derived from intestinal epithelial cells treated with SC06 (Ba) and investigated the regulation of Mφ phagocytosis, apoptosis, and polarization. We isolated two exosomes from intestinal porcine epithelial cell lines (IPEC-J2) with or without Ba-treatment, named Ba-Exo and Exo, respectively. They had typical sizes and a cup-shaped morphology, and their surfaces presented typical exosomes-associated proteins, including CD63, ALIX, and TSG101. Ba-Exo and Exo could entrer Mφ (3D4/21 cells) effectively. Moreover, an phagocytosis assay demonstrated that Ba-Exo can promote phagocytosis of Mφ. Similar to Exo, Ba-Exo had no effect on Mφ apoptosis. Furthermore, Ba-Exo significantly increased inducible nitric oxide synthase (iNOS), declined the expression of arginase 1 (Arg1) in Mφ, and stimulated Mφ polarization to M1. To explore the differences in the regulation of Mφ polarization between Ba-Exo and Exo, we performed reverse transcription quantitative polymerase chain reaction analysis of the small RNAs and found that miR-222 increased in the Ba-Exo group compared to that in the Exo group. These results provide a new perspective on the relationship between probiotics and intestinal immunity.
Xiaogang Xu, Rongrong Liu, Xuqiang Zhou, Zhongshan Zhang, Tianjun Zhu, Yingying Huang, Lan Chai, Yazhen Wang, Zhenlei Zhao, Weifen Li, Genxiang Mao

2432 related Products with: Characterization of exosomes derived from IPEC-J2 treated with probiotic SC06 and its regulation of macrophage functions.

5 G100ug150 ug10 mg200 5 per Sleeve, 100 Flasks/100 µg100ug50 ug 2ug

Related Pathways