PIPET,SERO,TD,SHORTY,MULTI,ORN,10ML
- Known as:
- PIPET,SERO,TD,SHORTY,MULTI,ORN,10ML
- Catalog number:
- 72110-10210
- Product Quantity:
- 200
- Category:
- -
- Supplier:
- Kimb
- Gene target:
- PIPET SERO SHORTY MULTI ORN 10ML
Related genes to: PIPET,SERO,TD,SHORTY,MULTI,ORN,10ML
- Gene:
- IL3 NIH gene
- Name:
- interleukin 3
- Previous symbol:
- -
- Synonyms:
- IL-3, MULTI-CSF, MCGF, MGC79398, MGC79399
- Chromosome:
- 5q31.1
- Locus Type:
- gene with protein product
- Date approved:
- 2001-06-22
- Date modifiied:
- 2015-07-06
Related products to: PIPET,SERO,TD,SHORTY,MULTI,ORN,10ML
Related articles to: PIPET,SERO,TD,SHORTY,MULTI,ORN,10ML
- IL-3/STAT5 signaling pathway is crucial for the development and activation of immune cells, contributing to the cellular response to infections and inflammatory stimuli. Dysregulation of the IL-3/STAT5 signaling have been associated with inflammatory and autoimmune diseases characterized by inflammatory cell infiltration and organ damage. IL-3 receptor α (IL-3Rα) specifically binds to IL-3 and initiates intracellular signaling, resulting in the phosphorylation of STAT5. However, the regulatory mechanisms of IL-3Rα remain unclear. Here, we identified the E3 ubiquitin ligase RNF128 as a negative regulator of IL-3/STAT5 signaling by targeting IL-3Rα for lysosomal degradation. RNF128 was shown to selectively bind to IL-3Rα, without interacting with the common beta chain IL-3Rβ, which shares the subunit with GM-CSF. The deficiency of Rnf128 had no effect on GM-CSF-induced phosphorylation of Stat5, but it resulted in heightened Il-3-triggered activation of Stat5 and increased transcription of the Id1, Pim1, and Cd69 genes. Furthermore, we found that RNF128 promoted the K27-linked polyubiquitination of IL-3Rα in a ligase activity-dependent manner, ultimately facilitating its degradation through the lysosomal pathway. RNF128 inhibited the activation and chemotaxis of macrophages in response to LPS stimulation, thereby attenuating excessive inflammatory responses. Collectively, these results reveal that RNF128 negatively regulates the IL-3/STAT5 signaling pathway by facilitating K27-linked polyubiquitination of IL-3Rα. This study uncovers E3 ubiquitin ligase RNF128 as a novel regulator of the IL-3/STAT5 signaling pathway, providing potential molecular targets for the treatment of inflammatory diseases. - Source: PubMed
Publication date: 2024/05/03
Yu JinggeLi JianguoShen AoLiu ZhipingHe Tian-Sheng - Certain oncogenes, including mutant RAS and BRAF, induce a type of senescence known as oncogene-induced senescence (OIS) in normal cells in a cell-type-specific manner. OIS serves as a barrier to transformation by activated oncogenes. Our previous studies showed that mutant KRASV12 did not efficiently induce OIS in an hTERT / Cdk4-immortalized normal human bronchial epithelial cell line (HBEC3), but it did enhance both anchorage-dependent and anchorage-independent growth. In this study, we investigated whether mutant BRAF, a well-known inducer of OIS, could trigger OIS in HBEC3 cells. We also assessed the impact of mutant BRAF on the growth of HBEC3 cells, as no previous studies have examined this using a normal bronchial epithelial cell line model. We established an HBEC3 cell line, designated as HBEC3-BIN, that expresses mutant BRAF in a doxycycline-regulated manner. Unlike our previous finding that KRASV12 upregulated both pERK and pAKT, mutant BRAFV600E upregulated pERK but not pAKT in HBEC3-BIN cells. Similar to KRASV12, BRAF did not efficiently induce OIS. Interestingly, while BRAF inhibited colony formation in anchorage-dependent conditions, it dramatically enhanced colony formation in anchorage-independent conditions in HBEC3-BIN. In HBEC3 cells without BRAF or KRASV12 expression, p21 was only detected in the cytoplasm, and its localization was not altered by the expression of BRAF or KRASV12. Next-generation sequencing analysis revealed an enrichment of gene sets known to be involved in carcinogenesis, including IL3/JAK/STAT3, IL2, STAT5, and the EMT pathway. Our results indicate that, unlike KRAS, which promoted both, BRAF enhances anchorage-independent growth but inhibits anchorage-dependent growth of HBEC3. This contrast may result from differences in activation signaling in the downstream pathways. Furthermore, HBEC3 cells appear to be inherently resistant to OIS, which may be partly due to the fact that p21 remains localized in the cytoplasm upon expression of BRAF or KRASV12. - Source: PubMed
Publication date: 2024/04/26
Muraki NaoKawabe NozomiOhashi AyanoUmeda KannaKatsuda MasahitoTomatsu AyaYoshida MikinaKomeda KazukiMinna John DTanaka IchidaiMorise MasahiroMatsushima MiyokoMatsui YusukeKawabe TsutomuSato Mitsuo - Embolic materials currently in use for portal vein embolization (PVE) do not treat the tumor, which poses a risk for tumor progression during the interval between PVE and surgical resection. Here, we developed an ionic-liquid-based embolic material (LEAD) for portal vein embolization. After synthesizing and evaluating ionic liquids (ILs) at different molar ratios, IL3:1 emerged as the optimal candidate based on its superior diffusion of solubilized chemotherapy drugs and near-infrared drug surrogates through tissue-like matrices, alongside significant cytotoxicity against cholangiocarcinoma and hepatocellular carcinoma cells, proving its suitability for the LEAD formulation. LEAD was further optimized and characterized for diffusivity, X-ray visibility, and cytotoxicity for in vivo use. In the porcine renal embolization model, LEAD delivered from the main renal artery reached vasculature down to 10 microns with uniform tissue ablation and delivery of small and large therapeutics. In non-survival and survival porcine experiments, successful PVE was achieved in minutes, leading to the expected chemical segmentectomy, and delivery of a large protein drug (i.e., Nivolumab) with LEAD. In cholangiocarcinoma mouse tumor models and in ex vivo human tumors, LEAD consistently achieved an effective ablation and wide drug distribution. Furthermore, various strains of drug-resistant patient-derived bacteria showed significant susceptibility to LEAD, suggesting that LEAD may also prevent infectious complications resulting from tissue ablation. With its capabilities to embolize, ablate, and deliver therapeutics, ease of use, and a high safety profile demonstrated in animal studies, LEAD offers a potential alternative to tumor ablation with or without PVE for FLR growth. This article is protected by copyright. All rights reserved. - Source: PubMed
Publication date: 2024/04/27
Cevik EnesAlbadawi HassanZhang ZefuDemirlenk YusufAtar DilaKeum ChrisKim JinjooGraf ErinGunduz SeydaRehman SulimanOklu Rahmi - Secreted deoxyribonucleases (DNases), such as DNase-1 and DNase-IL3, degrade extracellular DNA, and endogenous DNases have roles in resolving airway inflammation and guarding against autoimmune responses to nucleotides. Subsets of patients with asthma have high airway DNA levels, but information about DNase activity in health and in asthma is lacking. To characterize DNase activity in health and in asthma, we developed a novel kinetic assay using a Taqman probe sequence that is quickly cleaved by DNase-I to produce a large product signal. We used this kinetic assay to measure DNase activity in sputum from participants in the Severe Asthma Research Program (SARP)-3 (n=439) and from healthy controls (n=89). We found that DNase activity was lower than normal in asthma (78.7 RFU/min vs 120.4 RFU/min, p<0.0001). Compared to asthma patients with sputum DNase activity levels in the upper tertile activity levels, those in the lower tertile of sputum DNase activity were characterized clinically by more severe disease and pathologically by airway eosinophilia and airway mucus plugging. Carbamylation of DNase-I, a post translational modification that can be mediated by eosinophil peroxidase, inactivated DNase-I. In summary, a Taqman probe-based DNase activity assay uncovers low DNase activity in the asthma airway which is associated with more severe disease and airway mucus plugging and may be caused, at least in part, by eosinophil-mediated carbamylation. - Source: PubMed
Publication date: 2024/04/23
Charbit Annabelle RLiegeois Maude ARaymond Wilfred WComhair Suzy A AJohansson Mats WHastie Annette TBleecker Eugene RFajt MerrittCastro MarioSumino KaharuErzurum Serpil CIsrael ElliotJarjour Nizar NMauger David TMoore Wendy CWenzel Sally EWoodruff Prescott GLevy Bruce DTang Monica CFahy John V - AML is characterized by mutations in genes associated with growth regulation such as internal tandem duplications (ITD) in the receptor kinase FLT3. Inhibitors targeting FLT3 (FLT3i) are being used to treat patients with FLT3-ITD+ but most relapse and become resistant. To elucidate the resistance mechanism, we compared the gene regulatory networks (GRNs) of leukemic cells from patients before and after relapse, which revealed that the GRNs of drug-responsive patients were altered by rewiring their AP-1-RUNX1 axis. Moreover, FLT3i induces the upregulation of signaling genes, and we show that multiple cytokines, including interleukin-3 (IL-3), can overcome FLT3 inhibition and send cells back into cycle. FLT3i leads to loss of AP-1 and RUNX1 chromatin binding, which is counteracted by IL-3. However, cytokine-mediated drug resistance can be overcome by a pan-RAS inhibitor. We show that cytokines instruct AML growth via the transcriptional regulators AP-1 and RUNX1 and that pan-RAS drugs bypass this barrier. - Source: PubMed
Publication date: 2024/03/26
Coleman Daniel J LKeane PeterChin Paulynn SAmes LukeKellaway SophieBlair HelenKhan NaeemGriffin JamesHolmes ElizabethMaytum AlexanderPotluri SandeepStrate LaraKoscielniak KingaRaghavan ManojBushweller JohnHeidenreich OlafRabbitts TerryCockerill Peter NBonifer Constanze