593 Results for: "Adipogen"

Supplier: Adipogen

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.

Supplier: Adipogen

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.

Supplier: Adipogen

Methylglyoxal (MG), an endogenous metabolite that increases in diabetes and is a common intermediate in the Maillard reaction (glycation), reacts with proteins and forms advanced glycation end products (AGE). MG reacts with arginine residue in protein and forms numerous numbers of adducts, such as argpyrimidine.

Supplier: Adipogen

The inflammatory actions of IL-1alpha and beta depend on their interaction with its receptor, IL-1R1, and can be negatively controlled by several inhibitors such as IL-1Ra, IL-1R type 2 (IL-1R2), SIGIRR and the soluble form of IL-1 receptor accessory protein (IL-1RAcP). IL-1R2 neutralizes IL-1 either as a surface decoy receptor or in a cleaved and secreted form. IL-1R2 is expressed on B cells, on neutrophils and on in vitro expanded human Tregs.

Supplier: Adipogen

HMGB1 was originally discovered as an essential DNA-binding protein for regulating p53, NF-kappaB and other important proteins. It is secreted from activated dentric cells, macrophage and nectrotic cells, and acts as a ligand for RAGE, TLR-2 and TLR-4 expressed on surrounding cells. As a result, HMGB1 activates Rac, CDC42 and NF-kappaB inducing localized innate immunity of damaged tissue, tissue regeneration by recruitment of stem cells and hemostasis by induction of tissue factor expression. HMGB1 is also a causative agent of various diseases as it causes localized inflammation such as arteriosclerosis, chronic rheumatoid arthritis and nephritis. Anti-HMGB1, mAb (recombinant) (Giby-1-4) (Biotin) is an antibody developed by antibody phage display technology using a human naive antibody gene library. These libraries consist of scFv (single chain fragment variable) composed of VH (variable domain of the human immunoglobulin heavy chain) and VL (variable domain of the human immunoglobulin light chain) connected by a polypeptide linker. The antibody fragments are displayed on the surface of filamentous bacteriophage (M13). This scFv was selected by affinity selection on antigen in a process termed panning. Multiple rounds of panning are performed to enrich for antigen-specific scFv-phage. Monoclonal antibodies are subsequently identified by screening after each round of selection. The selected monoclonal scFv is cloned into an appropriate vector containing a Fc portion of interest and then produced in mammalian cells to generate an IgG like scFv-Fc fusion protein.

Supplier: Adipogen

Human CD279 (PD-1; Programmed Cell Death 1) is a 55 kD Ig superfamily member with similarity to CD28 and CD152 (CTLA-4). It is expressed on activated T and B and myeloid cells and engagement by its ligands PD-L1 (CD274; B7-H1) or PD-L2 (B7-DC) can inhibit proliferation and cytokine expression. In mice blockade of PD-1 ligand interaction has been used to augment T cell anti-cancer responses.

Supplier: Adipogen

TIE-2 acts as cell-surface receptor for ANGPT1, ANGPT2 and ANGPT4 and regulates angiogenesis, endothelial cell survival, proliferation, migration, adhesion and cell spreading, reorganization of the actin cytoskeleton, but also maintenance of vascular quiescence. It has anti-inflammatory effects by preventing the leakage of proinflammatory plasma proteins and leukocytes from blood vessels. It is required for normal angiogenesis and heart development during embryogenesis and for post-natal hematopoiesis. After birth, it activates or inhibits angiogenesis, depending on the context. It inhibits angiogenesis and promotes vascular stability in quiescent vessels, where endothelial cells have tight contacts. In migrating endothelial cells that lack cell-cell adhesions, ANGT1 recruits TEK to contacts with the extracellular matrix, leading to the formation of focal adhesion complexes, activation of PTK2/FAK and of the downstream kinases MAPK1/ERK2 and MAPK3/ERK1 and ultimately to the stimulation of sprouting angiogenesis.

Supplier: Adipogen

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.

Supplier: Adipogen

Procaspase-8 belongs to the family of caspases. Binding of FasL to Fas leads to formation of a receptor complex at the cellular membrane, which was named DISC. The DISC consists of oligomerized receptors, the DD-containing adaptor molecule FADD, procaspase-8, procaspase-10 and c-FLIP. The DISC structure provides a platform for the oligomerization of procaspase-8 that allows two procaspase-8 homodimers to be in the close proximity leading to the initial activation of procaspase-8. At the first cleavage step, the N-terminal p43/p41 and the C-terminal p30 cleavage products are generated. Importantly, these cleavage products already possess catalytic activity. At the second cleavage step, p43/p41 and p30 are processed to p10 and p20, respectively, which leads to the generation of the active caspase-8 heterotetramer (p20/p10)2.

Supplier: Adipogen

Mouse T cell immunoglobulin and mucin domain-containing protein 4, also known as T cell membrane protein 4, TIMD4 and TIM4 is a single-pass type I membrane protein which belongs to the immunoglobulin superfamily and TIM family. TIM4 contains one Ig-like V-type (immunoglobulin-like) domain. It is expressed on dendritic cells and macrophages. TIM4 plays an important role in the proliferation of T helper type 2 (Th2) cells. TIM4 is involved in regulating T cell proliferation and lymphotoxin signaling. It is a ligand for HAVCR1 / TIMD1. The expression of TIM4 in fibroblasts enhanced their ability to engulf apoptotic cells. TIM4 and TIM1 are phosphatidylserine receptors for the engulfment of apoptotic cells and may also be involved in intercellular signaling in which exosomes are involved. Modulation of TIM4 production in dendritic cells (DCs) represents a novel therapeutic approach for the treatment of peanut allergy.

Supplier: Adipogen

IL-38 (IL-1F10) belongs to the IL-1 family of proteins. IL-38 is expressed in heart, placenta, fetal liver, spleen, thymus and tonsil. The expression in a variety of immune tissues and similarity to IL-1Ra suggest a role of IL-38 as a IL-1 family receptor antagonist. Il-38 inhibits IL-36 signaling by binding to IL-1R6. IL-38 (aa 20-152) is released from apoptotic cells to limit inflammatory macrophage and downstream Th17 activation by blocking IL1RAPL1 (Interleukin-1 receptor accessory protein-like 1, TIGIRR-2) signaling. IL-38 is unregulated during some autoimmune diseases such as Systemic Lupus Erythematosus.

Supplier: Adipogen

CD273 (B7-DC; PD-L2) is a type I surface molecule with homology to CD80, CD86, CD274. It is expressed primarily by dendritic cells and provides a stimulatory signal to CD279 (PD-1; programmed death molecule) which has an important immunoregulatory role by downregulating the T cell response. CD273 binds to CD279 (PD-1) with a 2-6 fold higher affinity than CD274.

Supplier: Adipogen

Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) are closely related secreted ligands which bind with similar affinity to Tie-2. Tie-2 and angiopoietins have been shown to play critical roles in embryogenic angiogenesis and in maintaining the integrity of the adult vasculature. Ang-1 activates Tie-2 signaling on endothelial cells to promote chemotaxis, cell survival, cell sprouting, vessel growth and stabilization. Ang-2 has been identified as a secreted protein ligand of Tie-2 and has alternatively been reported to be an antagonist for Ang-1 induced Tie-2 signaling as well as an agonist for Tie-2 signaling, depending on the cell context.

Supplier: Adipogen

DNER is an activator of the Notch1 pathway. It mediates neuron-glia interaction during astrocytogenesis.

Supplier: Adipogen

Potent protein kinase VEGFR2 inhibitor (2nm range). Binds to the pseudokinase domain of MLKL and blocks cell death by necroptosis, as well. With regards to its role in necroptosis, it is an ATP-mimetic that was shown to bind recombinant mouse MLKL pseudokinase domain, which showed inhibited TSQ-induced death of mouse dermal fibroblasts by delaying MLKL translocation to the membrane. Appears therefore to be a valuable reagent to inhibit necroptosis. It also provides an important proof-of-principle that targeting catalytically-dead pseudoenzymes represents a feasible, emerging therapeutic avenue.

Supplier: Adipogen

FMS-like tyrosine kinase 3 ligand (FLT3L) acts as a growth factor that increases the number of immune cells (lymphocytes (B cells and T cells)) by activating the hematopoietic progenitors. It binds to FLT3 (CD135) which is found on multipotent progenitor (MPP) and common lymphoid progenitor (CLP) cells in mice. FLT3L induces the mobilization of the hematopoietic progenitors and stem cells in vivo which may help the system to kill cancer cells. FLT3L is crucial for steady-state pDC (plasmacytoid dendritic cells) and cDC (classical dendritic cells) development. Deficiency of FLT3L causes a dramatic decrease in DC numbers, whereas increasing its availability increase in DC numbers.

Supplier: Adipogen

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.

Supplier: Adipogen

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.

Supplier: Adipogen

Human CD66b (CEACAM8, CGMb, NCA-95, CD67) is a 95kD member of the Carcinoembryonic Antigen (CEA) group. It is expressed on granulocytes and functions as an adhesion molecule. Similar to the CD66 a, c, and d isoforms, engagement of CD66b on neutrophils causes increased adhesion to endothelial cells. Crosslinking CD66b on neutrophils with antibodies triggers IL-8 release.

Supplier: Adipogen

NAD kinase catalyzes the transfer of a phosphate group from ATP to NAD+ to generate NADP+, which in its reduced form acts as an electron donor for biosynthetic reactions

Supplier: Adipogen

Caspase-2 is a Class I caspase with a long prodomain necessary for nuclear localization. Upon activation of the apoptotic pathway, the procaspase is cleaved into smaller fragments. Caspase-2 is the nuclear apoptotic respondent to cellular genotoxic stress or mitotic catastrophe and is involved in the activation cascade of caspases responsible for apoptosis execution. Activation occurs upon recruitment to a complex containing a p53-induced death domain protein, PIDD. This suggests caspase-2 can be a nuclear initiator caspase with a requirement for caspase-9 and caspase-3 activation in downstream apoptotic events. In apoptotic pathways resulting from UV-induced DNA damage, processing of caspase-2 occurs downstream of mitochondrial dysfunction and of caspase-9 and caspase-3 activation, extending a possible role for caspase-2 as a parallel effector caspase.

Supplier: Adipogen

Remazol brilliant blue-dyed galactomannan polysaccharide. Soluble substrate for the specific measurement of endo-1,4-beta-D-mannanase/galactomannase. Used for the measurement of enzyme activity, for research, biochemical enzyme assays and in vitro diagnostic analysis.

Supplier: Adipogen

Fibroblast growth factor 21 (FGF-21) is a member of the fibroblast growth factor family and has been identified as an important regulator of energy metabolism connecting nutrition, growth, reproduction and longevity. FGF-21 lacks the heparin-binding domain of most FGF proteins, allowing its secretion. FGF-21 is abundantly expressed in adipose tissues, liver and pancreas. In adipose tissue, FGF-21 promotes glucose uptake and oxidation and in liver it replenishes on fasting the tissues with fuel on low nutritional supply. It also induces lipolysis and ketogenesis. FGF-21 acts through FGF receptors (FGFR) associated with the auxiliary protein beta-Klotho. Recently, FGF-21 has been reported to interact directly with the brain circadian clock to coordinate activity and reproduction as part of the adaptation to fasting. Due to its multiple functions of normalizing glucose, lipid and energy homeostasis, FGF-21 represents an attractive novel therapy for type 2 diabetes mellitus and obesity.

Supplier: Adipogen

Irisin is a recently described exercise-induced hormone secreted by skeletal muscle in mice and humans. Irisin activates beige fat cells (beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone Irisin). Irisin is cleaved from the type I membrane protein FNDC5 and improves systemic metabolism by increasing energy expenditure.

Supplier: Adipogen

Human CD155 (Polio Virus Receptor, PVR, Necl-5) is a 70kd type I Ig superfamily molecule. It is involved in formation of intracellular junctions between epithelial cells. Its ligands include CD226 (DNAM-1), and CD96 (TACTILE). CD155 expression by tumor has been shown to be upregulated by nitric oxide. A soluble version of CD155 has been shown to exist. High CD155 expression has recently been exploited to use engineered poliovirus to treat glioblastoma.

Supplier: Adipogen

Bim belongs to the Bcl-2 protein family. Bcl-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the Bcl-2 protein family (BCL2, BCL2L1/BCL-X(L) and MCL1) and to act as an apoptotic activator, inducing apoptosis and anoikis. Several variants have been identified. The isoforms vary in cytotoxicity with isoform BimS being the most potent and isoform BimEL being the least potent.

Supplier: Adipogen

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.

Supplier: Adipogen

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.

Supplier: Adipogen

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.

Supplier: Adipogen

Progranulin (PGRN) is a widely expressed pluripotent growth factor which plays a role in processes such as development, wound repair and inflammation by activating signaling cascades that control cell cycle progression and cell motility. Its function in the central nervous system is of interest, as mutations in the PGRN gene were found in cases of frontotemporal degeneration (FTLD). In addition, PGRN has also been linked to tumorigenesis. Progranulin is a biomarker for FTLD, other types of Alzheimer‘s Disease (AD) and potentially for MCI (Mild Cognitive Impairment). Additionally, PGRN is described as a new ligand of TNF receptors and a potential therapeutic against inflammatory disease like arthritis.