You Searched For: 2-Hydroxyquinoline-4-carboxylic acid


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Description: Unmethylated CG dinucleotides within particular sequence contexts are responsible for the immunostimulatory activity of bacterial DNA. Synthetic oligonucleotides (ODN) that contain such CpG motifs (CpG ODNs) mimic microbial DNA. The innate immune system of vertebrates has the ability to recognize CpG motifs in microbial DNA via the Toll-like receptor (TLR) 9 if the CpG ODN were free of additional immune stimulatory contaminants often present in synthetic commercial CpG ODN preparations designed for molecular biology applications (i.e. PCR). Given that high quality CpG ODNs were used, a close link has been established between the expression of TLR9 on certain immune cell subsets and the modulation of the immune system by CpG DNA. Different types of CpG ODNs were identified based on their differing biological effects on different cell types: ODN Type A is a potent inducer of IFN-alpha in human PDC, (i.e. ODN 1585 or 2216) leading to antigen presenting cell (APC) maturation, whereas ODN Type B (i.e. ODN 2006 or ODN 1668 / ODN 1826) is a weak inducer of IFN-alpha but rather stimulates IL-8 production and increasing costimulatory and Ag-presenting molecules and triggers proliferation of B-cells and IgM and IL-6 production. A third type of CpG ODN has been identified, termed ODN Type C, with both high induction of INF-alpha in PDC and activation of B-cells. The sequence of CpG Type C (also called K) (i.e. ODN 2395 or M362) combines elements of both Type A and Type B and contains a central palindromic sequence with CG dinucleotides, a characteristic feature of Type A, and a TCGTCG motif at the 5' end, present in Type B CpG ODNs. Although the CpG motifs are thought to differ between mice and humans, in both species the recognition of CpG ODNs is mediated by TLR9. The optimal CpG motif in humans is GTCGTT and GACGTT for the murine sequence. However, recent evidence suggests that this sequence specificity is restricted to phosphorothioate (PS)-modified ODN and is not observed when a natural phosphodiester backbone is used. In recent years sequence requirements, specificity, signalling pathways and kinetics of the TLR9 suppression by inhibitory ODNs (iODNs) have been investigated.
Catalog Number: 102981-416
Supplier: Adipogen


Description: BAFF is mainly produced by innate immune cells such as neutrophils, monocytes, macrophages, dendritic cells, follicular dendritic cells. T cells, activated B cells, some malignant B cells and also non-lymphoid cells like astrocytes, synoviocytes and epithelial cells can also produce BAFF. BAFF binds three distinct receptors (BAFF-R, TACI and BCMA) expressed predominantly on B cells, although activated T cells also express BAFF-R. BAFF is a master regulator of peripheral B cell survival, and together with IL-6, promotes Ig class-switching and plasma cell differentiation. Besides its major role in B cell biology, BAFF co-stimulates activated T cells. Deregulated expression of BAFF leads to autoimmune disorders in mice. In humans, elevated levels of soluble BAFF have been detected in the serum of patients with various autoimmune diseases such as Sjoegren syndrome, Rheumatoid arthritis (RA), Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE). BAFF has also increased levels in some lymphoid cancers. Processed human BAFF can either remain as a trimer, which is usual for TNF family ligands or assemble into 60-mer composed of 20 trimers. Mouse BAFF 60-mer has been identified in the serum of BAFF transgenic mice. Oligomerization of BAFF 3-mer into 60-mer in human BAFF is prevented by mutation of His218, a residue critical for 3-mer-to-3-mer interactions, but not for receptor binding. Despite the predominant functional role of processed BAFF in vivo, membrane-bound BAFF might also play a role. Indeed, soluble BAFF (3-mer) can trigger BAFF-R but not TACI or BCMA, whereas oligomeric forms of BAFF (BAFF 60-mer), which mimic membrane-bound BAFF, activate all BAFF receptors.
Catalog Number: 102980-174
Supplier: Adipogen


Description: Podoplanin is expressed on glomerular epithelial cells (podocytes), type I lung alveolar cells, lymphatic endothelial cells and numerous tumors, including colorectal tumors, squamous cell carcinomas, testicular seminoma and brain tumors. Podoplanin is the ligand for C-type lectin-like receptor 2 (CLEC-2). Their association is dependent on sialic acid on O-glycans of podoplanin. Through its association with CLEC-2, podoplanin induces platelet aggregation and tumor metastasis. Podoplanin is also necessary for lymphatic vessel formation, normal lung cell proliferation and alveolus formation at birth.
Catalog Number: 102978-598
Supplier: Adipogen


Description: PARP-2 is involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.
Catalog Number: 102980-362
Supplier: Adipogen


Description: PAG is a ubiquitously expressed transmembrane adapter protein. Depending on its phosphorylation status, it appears as diffuse band(s) of 80-90kDa by SDS-PAGE, with phosphorylation leading to a shift towards a higher apparent molecular mass. Tyrosine phosphorylated PAG recruits Csk to the membrane and negatively regulates Src family kinases via Csk-mediated phosphorylation. Upon T cell receptor engagement, PAG becomes dephosphorylated, thereby displacing Csk from the membrane and enabling the activation of the Src kinases Fyn and Lck. PAG negatively regulates TCR (T cell antigen receptor)-mediated signaling in T cells and FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. It promotes CSK activation and recruitment to lipid rafts, which results in LCK inhibition. It inhibits immunological synapse formation by preventing dynamic arrangement of lipid raft proteins and may be involved in cell adhesion signaling.
Catalog Number: 102979-976
Supplier: Adipogen


Description: Interleukin-4 (IL-4) is a cytokine produced by type 2 helper T cells, the Th2 cells. These cells tends to make a specific set of lymphokines including IL-4, IL-5, IL-6, IL-10, IL-13, IL-3 and GM-CSF and fail to produce IL-2, IFN-gamma, and lymphotoxin (TNF-beta). In addition, mast cells can produce IL-4. IL-4 exerts numerous effects on various hematopoietic cell types. On B cells, IL-4 promotes immunoglobulin class switching to IgE and IgG1 isotypes and upregulates MHC class II and CD23 expression. IL-4 promotes survival, growth, and differentiation of both T and B lymphocytes, mast cells and endothelial cells. In addition, IL-4 inhibits the production of TNF, IL-1, and IL-6 by macrophages.
Catalog Number: 102981-584
Supplier: Adipogen


Description: Betatrophin (RIFL; Lipasin; Angiopoietin-like protein 8 (ANGPTL8)) is a newly discovered secreted protein of 198 aa that was proposed to promote beta cell proliferation and improve glucose tolerance in mice. Betatrophin may also function in inhibition of lipase activity and on serum triglyceride regulation. Betatrophin is expressed in the liver and in white and brown adipose tissue of mice. In humans, betatrophin is found to be predominantly expressed in the liver. Betatrophin levels are reduced by fasting and are elevated upon insulin resistance and during pregnancy. Betatrophin, according to preliminary data could bind to the macrophage receptor Marco and also to RTN4R, a neuronal receptor. Recently, a study using ANGPTL8 KO mice showed that ANGPTL8/Betatrophin does not play a role in beta cell proliferation nor in glycemic control as previously thought, but regulates plasma triglyceride levels.
Catalog Number: 102980-290
Supplier: Adipogen


Description: Activation of cells by LPS is mediated by the Toll-like receptor 4 (TLR4). For optimal interaction with LPS, TLR4 requires association with myeloid differentiation protein 2 (MD-2). According to current consensus activation of TLR4 is preceded by the transfer of LPS to membrane-bound (m) or soluble (s) CD14 by LPS-binding protein (LBP). Re-form LPS and lipid A, but not S-form LPS, are capable of inducing TNF-alpha responses also in the absence of CD14. LPS, synthesized by most wild-type (WT) Gram-negative bacteria (S-form LPS), consists of three regions, the O-polysaccharide chain, which is made up of repeating oligosaccharide units, the core oligosaccharide and the lipid A, which harbors the endotoxic activity of the entire molecule. R-form LPS synthesized by the so-called rough (R) mutants of Gram-negative bacteria lacks the O-specific chain. Furthermore, the core-oligosaccharide may be present in different degrees of completion, depending on the class (Ra to Re) to which the mutant belongs. LPS are amphipathic molecules whose hydrophobicity decreases with increasing length of the sugar part. Based upon these differences, S- and R-form LPS show marked differences in the kinetics of their blood clearance and cellular uptake as well as in the ability to induce oxidative burst in human granulocytes and to activate the host complement system.
Catalog Number: 102981-346
Supplier: Adipogen


Description: LSD1 is a promising target for cancer therapy. Epigenetic control of histone methylation is frequently associated with oncogenesis and LSD1 is overexpressed in many types of cancer. siRNA knockdown of LSD1 has been shown to suppress growth of cancer cells. SP-2528 is a selective and reversible LSD1 inhibitor with an IC(50) of 10nM. SP-2528 demonstrates a high specificity for LSD1, with no effect on MAOi.
Catalog Number: 102979-856
Supplier: Adipogen


Description: Neuregulin-4 (Nrg4) belongs to a small family of EGF-like (EGFL) domain-containing proteins that are synthesized as transmembrane precursors and undergo proteolytic cleavage. The EGF-like domain (aa 5-46) of Nrg4 (aa 1-53) directly binds to the receptors ErbB3 and 4. Nrg4 is a cold induced adipokine, highly expressed in adipose tissues and enriched in brown fat. It is increased during brown adipocyte differentiation and reduced in rodent and human obesity. It promotes neurite outgrowth and protects against diet-induced insulin resistance and hepatic steatosis through attenuating hepatic lipogenic signaling. This hepatic effect of Nrg4 is mediated by ErbB3 and ErbB4 signaling that negatively regulates de novo lipogenesis mediated by LXR and SREBP1c. This effect of Nrg4 on fatty liver and insulin resistance could lead to the development of Nrg4 as an effective therapeutic biological for the treatment of NAFLD and type 2 diabetes. GST-Nrg4 (aa 1-53) recombinant protein has been shown to mimic the effect of endogenous secreted Nrg4 on liver lipogenesis.
Catalog Number: 102980-338
Supplier: Adipogen


Description: IL-36alpha (IL-1F6), IL-36beta (IL-1F8) and IL-36gamma (IL-1F9) bind to IL-36R (IL-1Rrp2) and IL-1RAcP, activating similar intracellular signals as IL-1. IL-36Ra inhibits the production of proinflammatory cytokines, including IL-12, IL-1beta, IL-6, TNF-alpha and IL-23 induced by IL-36 in BMDC and CD4 T cells. Skin and dendritic cells are targets of the IL-36 interleukins leading to a Th1 response. These cytokines may represent potential targets for immune-mediated inflammatory conditions or, alternatively, could be used as adjuvants in vaccination.
Catalog Number: 102979-946
Supplier: Adipogen


Description: Asc promotes caspase-mediated apoptosis. This proapoptotic activity is mediated predominantly through the activation of caspase-9. It is a component of the inflammasome, a protein complex which also includes NLRP3/NALP3, CARD8 and CASP1 and whose function is the activation of proinflammatory caspases.
Catalog Number: 102979-930
Supplier: Adipogen


Description: Acrolein (ACR) is a representative carcinogenic aldehyde found ubiquitously in the environment and formed endogenously through oxidation reactions, such as lipid peroxidation and myeloperoxidasecatalyzed amino acid oxidation. ACR is highly reactive aldehyde and reacts with lysine residue in protein. The reaction with ACR and lysine residue leads to the formation of numerous numbers of adducts, such as formyl-dehydropiperidino-lysine (FDP-lysine) type derivative.
Catalog Number: 102979-298
Supplier: Adipogen


Description: Notch signaling pathway regulates many different cell fate decisions in both vertebrate and invertebrate species. There are 5 canonical Notch ligands in mammals: Jagged-1, Jagged-2, DLL1, DLL3 and DLL4. These can bind to the four Notch receptors Notch 1-4. It is important for pattern formation during development such as neurogenesis, angiogenesis or myogenesis and regulates T cell development and stem cell maintenance. Notch signaling is also involved in cellular processes through-out adulthood. Signaling via Notch occurs between neighbouring cells and both the receptor and its ligands are transmembrane proteins.
Catalog Number: 102980-166
Supplier: Adipogen


Description: Cholesterol oxidation products, especially 7-Ketocholesterol (7KC), have been the focus of much attention because they are present in human atherosclerotic plaque and display a wide range of atherogenic properties in vitro and to some extant in vivo.
Catalog Number: 102981-718
Supplier: Adipogen


Description: In recent years several groups have studied the sequence requirements, specificity, signaling pathways and kinetics of the TLR (Toll-like receptor) 9 suppression by inhibitory oligonucleotide motifs, which led to a class of novel inhibitory oligonucleotide (iODNs), that is independent of the previously thought species preference. Subsequently it has been discovered that telomeric DNA repeats (TTAGGG)n can block immune activation by CpG-ODNs. Short, 11-15 base long oligonucleotides were synthesized that were capable of potently inhibiting CpG-stimulation. The optimal inhibitory DNA motif consists of a pyrimidine-rich triplet, preferably CCT, which is positioned 5- to the GGG sequence in a singlestranded DNA molecule. Additionally, both the optimal spacing between the CCT and GGG motifs, as well as their relative order to each other, is of crucial importance for the inhibitory DNA action. Interestingly, although both TLR7/TLR8 ligands and bacterial DNA share the endosomal compartment for receptor binding and signal transduction, certain iODNs (G-type) suppress only TLR9-mediated activation, whereas prototype class I iODN may also interfere with the activation via the TLR7/TLR8 pathway. Recently, intriguing evidence has been presented that for some iODN classes the immuno-modulatory biological activity shows only limited sequence dependency or may not even involve TLR-mediated uptake and signaling pathways. For example iODNs of the class II are thought to act on immune activation through inhibition of STAT signaling and independent of TLR signaling via binding to a yet to be identified 'ODN-receptor'. Slightly modified phosphodiester versions of the most potent inhibitory ODNs were also able to profoundly block the immune activation of macrophages and just recently prove to be valuable tools for in vivo use in experimental animal models of inflammatory and auto-immune diseases. Based upon these recent insights the following classification for iODNs has been suggested: Class I: G-stretch ODNs: TLR9-specific competitors, some iODNs may also affect TLR7 and TLR8 signalingClass II: ODNs with telomeric repeats: TLR-independent inhibitors of STAT signaling (cellular uptake via an 'ODN receptor'?)Class III: Inhibitors of DNA uptake in a sequence independent mannerClass IV: Long phosphorothioate ODNs as direct competitors of TLR9 signaling in a sequence independent manner
Catalog Number: 102981-400
Supplier: Adipogen


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