September 28, 2020
Gasdermin D Succination by Fumarate inactivates and blocks Pyroptosis
Inflammasomes are large multimolecular complexes involved in innate immunity that upon activation lead to cleavage of the pore forming protein Gasdermin D to promote inflammatory cell death, called pyroptosis.
Recently, the lab of Prof. Katherine A. Fitzgerald (University of Massachusetts Medical School, US) describes in the journal Science that a metabolite of aerobic glycolysis (Krebs’ cycle), fumarate, affects inflammatory responses by inhibiting cleavage of Gasdermin D and consequently pyroptotic cell death. Endogenous fumarate or dimethyl fumarate (DMF) delivered to cells, succinates a critical cysteine of Gasdermin D (GSDMD) to prevent its interaction with caspases, its oligomerization to form membrane pore and its capacity to induce cell death. Interestingly Gasdermin E, a Gasdermin D analog, is also inhibited by fumarate. This study explains the efficacy and the mechanism of action of dimethyl fumarate (called Tecfidera and approved by U.S. Food and Drug Administration) for the treatment of multiple sclerosis (MS).
AdipoGen Life Sciences provides the standard Caspase-1 antibodies used in this study:
Other reagents in the inflammasome field are also available from AdipoGen Life Sciences:
LIT: Succination inactivates gasdermin D and blocks pyroptosis: F. Humphries, et al.; Science 369, 1633 (2020)
September 22, 2020
Concanamycin A Enables Immune System to Kill HIV Infected Cells
Recently, the lab of Prof. Kathleen L. Collins (University of Michigan) has discovered an unexpected potential weapon against HIV protein. They describe in a new study a class of drugs that can help the immune system eliminate hard-to-kill cells infected with HIV. HIV can hide inside the human genome, lying dormant and ready to emerge at any time. HIV therefore establishes a persistent infection for which there is no cure, necessitating the development of new approaches to enhance the clearance of HIV-infected cells. HIV encodes Nef, which down-regulates MHC-I expression in infected cells to impair immune-mediated clearance by cytotoxic T lymphocytes. The plecomacrolide family of natural products has been identified as potent inhibitors of Nef, and concanamycin A (a lysosome inactivator) restored MHC-I and enhanced the clearance of HIV-infected primary cells by cytotoxic T lymphocytes. Concanamycin A counteracted Nef from diverse clades of HIV targeting multiple allotypes of MHC-I, indicating the potential for broad therapeutic utility.
AdipoGen Life Sciences is a manufacturer of high purity plecomacrolide antibiotics. All products are available in BULK quantities.
Concanamycin A (Prod. No. BVT-0237)
Concanamycin B (Prod. No. BVT-0253)
Concanamycin C (Prod. No. BVT-0254)
Bafilomycin A1 (Prod. No. BVT-0252)
Bafilomycin B1 (Prod. No. BVT-0004)
Bafilomycin C1 (Prod. No. BVT-0068)
LIT: Concanamycin A counteracts HIV-1 Nef to enhance immune clearance of infected primary cells by cytotoxic T lymphocytes: M.M. Painter, et al.; PNAS (2020)
September 08, 2020
Hyperforin counteracts Cytokine Storm in COVID-19
Pandemic coronavirus disease 2019 (COVID‐19), caused by SARS‐CoV‐2 virus, mainly affects adult or aging individuals with fever, dry cough and dyspnea of variable severity. In ~20% of patients, a widespread alveolar‐interstitial pneumonia develops with acute respiratory distress syndrome. With progression of the disease, when immune response or antiviral therapy fail to get rid of the virus, an excess release of pro‐inflammatory cytokines takes place (e.g., TNF‐α, IL‐1β, IL‐6, IFN‐γ, CXCL10, MCP‐1), the so called “cytokine storm,” eliciting extensive vasculitis, hyper‐coagulability and multi‐organ damage that, together with associated respiratory failure, represent the most common cause of death. Recently, the lab of Prof. Marta Menagazzi (University Verona) suggested that the Hypericum perforatum (St. John's Wort, SJW) extract and its main polyphenol component Hyperforin can, based on their anti-inflammatory activity of and their simultaneous blockade of multiple signaling pathways, such as IFN‐γ/IL‐1β/TNF‐α, JAK/STAT, NF‐κB and MAPK counteract cytokine storm during COVID-19.
LIT: Can Hypericum perforatum (SJW) prevent cytokine storm in COVID‐19 patients? P. Masiello, et al.; Phytother Res. 34, 1471 (2020)
April 14, 2020
NEW Panel of COVID-19 Research Products
AdipopGen Life Sciences launched its first panel of unique COVID-19 Research Products produced in our own facilities in Switzerland. Our landing page provides scientific insights and an overview on the product range related to SARS-CoV-2/COVID-19 research, featuring a unique ACE2 blocking antibody.
For more information visit https://adipogen.com/covid-19/
March 06, 2020
Glutamine Links Obesity to Inflammation
Obesity is defined as a chronic low-grade inflammation of the white adipose tissue and this inflammation is responsible for different obesity-linked pathologies and the onset of insulin resistance. The causative factors of white adipose tissue (WAT) inflammation during obesity remain unclear. A recent study published in Cell Metabolism by the lab of Prof. Mikael Ryden (Karolinska Institute, Sweden) now reports that the levels of glutamine in human white adipose tissue (WAT) are linked with obesity-associated inflammation. They observed that glutamine released from WAT is decreased during obesity and linked to larger fat cell size. This reduction of glutamine is due to reduction of glutamine synthetase (GLUL) and low GLUL expression is associated with pro-inflammatory pathways in human WAT. Interestingly, addition of glutamine in obese mice attenuates adipose tissue inflammation. Reduced glutamine levels during obesity shift the balance from glutaminolysis toward glycolysis, leading to nuclear O-GlcNAcylation, which activates inflammation. Glutamine is therefore a new player in inflammation in addition to its roles in cell proliferation and cancer.
AdipoGen Life Sciences provides multiple reagents in the immunometabolism and obesity field for in vitro and in vivo studies:
LIT: Glutamine Links Obesity to Inflammation in Human White Adipose Tissue: P. Petrus, et al.; Cell Metab. 31, 375 (2020)
January 20, 2020
VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance
VISTA (V-domain immunoglobulin suppressor of T cell activation) is a new negative checkpoint regulator homologous to PD-L1. VISTA potently suppresses T cell activation by binding to the receptor P-selectin glycoprotein ligand-1 (PSGL-1) at acidic pH. VISTA is the only negative checkpoint regulator expressed on naïve T cells where its precise function is not clear. A recent study published in Science by the labs of Prof. Randolph J. Noelle and Dr. Chao Cheng (School of Medicine at Dartmouth, Lebanon and Baylor College of Medicine, Houston, respectively) shows that VISTA expressed on naïve T cells acts as a brake for preventing a “homeostatic” conversion of naïve to effector T cells in response to self-antigen recognition. Blockade of the VISTA protein disrupts the major quiescent naïve T cell subset leading to increased frequencies of effector T cells and development of autoimmunity, while VISTA activation suppresses T cell immune responses by enhancing cell death of tolerogenic T cells. VISTA is the first immune checkpoint protein whose function is to enforce quiescence in naïve T lymphocytes in the absence of inflammation.
AdipoGen Life Sciences provides active proteins to study VISTA and PSGL-1 in vitro and in vivo:
LIT: VISTA is a checkpoint regulator for naïve T cell quiescence and peripheral tolerance: M.A. ElTanbouly, et al.; Science 367, 264 (eaay0524) (2020)
November 07, 2019
VISTA is an acidic pH-selective Ligand for PSGL-1
VISTA (V-domain immunoglobulin suppressor of T cell Activation) is type I Ig membrane protein homologous to PD-L1. VISTA is mainly expressed on hematopoietic tissues (spleen, thymus and bone marrow) and on myeloid cells. VISTA is a new negative checkpoint regulator that potently suppresses T cell activation. A recent study published in Nature by the lab of Dr. Alan J. Korman (Bristol-Myers Squibb) shows a new function of the protein P-selectin glycoprotein ligand-1 (PSGL-1) as a new receptor for the immune checkpoint VISTA. Multimer VISTA binds PSGL-1 expressed on leukocytes at acidic pH, but not at the physiological pH 7. VISTA - PSGL-1 interaction shows that immune response can be regulated by acidic environments found in tumors.
AdipoGen Life Sciences provides active proteins to study VISTA and PSGL-1 in vitro and in vivo:
LIT: VISTA is an acidic pH-selective ligand for PSGL-1: R.J. Johnston, et al.;Nature 574, 565 (2019)
October 29, 2019
Protective Role of Irisin in chronic Inflammatory Bowel Diseases (IBD)
Irisin is a protein cleaved from fibronectin type III domain-containing protein 5 (FNDC5) and has a beneficial role in adipose tissues, in brain and in bone remodelling. Chronic inflammation of the gut, such as inflammatory bowel disease (IBD), leads to osteoporosis and increased fractures. A recent study published in Scientific Reports by the lab of Prof. Susan Bloomfield (Texas A&M University) showed that injection of recombinant Irisin in a rat model of IBD mitigates inflammatory bone changes. Exogenous treatment with the recombinant Irisin protein from Adipogen Life Sciences (AG-40B-0103) improves bone formation rate and decreases the inflammatory status of bone. Irisin represents therefore a potential anti-inflammatory treatment against chronic diseases, such as IBD.
AdipoGen Life Sciences provides the best-in-class recombinant Irisin/FNDC5 proteins, antibody and ELISA kit to study Irisin and FNDC5 in vitro and in vivo:
LIT: DSS-induced colitis produces inflammation-induced bone loss while irisin treatment mitigates the inflammatory state in both gut and bone: C.E. Metzger, et al.; Sci. Rep. 9, 15144 (2019)
September 19, 2019
Protective role for IL-36 cytokines in obesity and metabolic disease
Interleukin-36α, β and γ (IL-36α, β and γ), members of the interleukin-1 (IL-1) family, are pro-inflammatory cytokines mainly involved in skin inflammatory diseases, but also in the inflammation of lung or gut. Recently, the lab of Prof. Patrick T. Walsh (Trinity College Dublin, Ireland) describes in Nature Communication a new protective role of the IL-36 family of cytokines in obesity and metabolic diseases. They observed that IL-36γ is increased in serum of obese patients with diabetes, indicating that elevated IL-36 cytokines may play a protective role in reducing blood sugar levels. IL-36 cytokines function by changing the composition of the intestinal microbiome towards a more metabolically healthy state. IL-36 cytokines enhance mucus-secretion from goblet cells in the colon, which promote the outgrowth of the commensal bacterial strain Akkermansia muciniphila, known to play an important protective role against obesity and metabolic dysfunction.
AdipoGen Life Sciences provides a Sensitive and Specific ELISA Kit to measure IL-36γ in serum/plasma:
AdipoGen Life Sciences is a Leader in the IL-36 Research field, providing a broad range of high quality ELISA Kits, Proteins and Antibodies:
... and many other IL-36-related Antibodies and Proteins!
LIT: Interleukin-36 cytokines alter the intestinal microbiome and can protect against obesity and metabolic dysfunction: F. Giannoudaki, et al.; Nat. Commun. 10, 4003 (2019)
September 12, 2019
Stress granules inhibit NLRP3 inflammasome activation by sequestering the helicase DDX3X
Inflammasomes are large multimolecular complexes involved in innate immune response and driving cell fate towards cell death, called pyroptosis. Stress granules are aggregates formed during cellular stress with pro-survival role composed of proteins and mRNA molecules. Recently, the lab of Prof. Thirumala-Devi Kanneganti (St. Jude Children's Research Hospital, Memphis) describes a new role of the stress granules in inhibiting the inflammasome. The stress granule protein DDX3X interacts with NLRP3 to activate the inflammasome. Assembly of stress granules leads to the sequestration of DDX3X, and thereby the inhibition of NLRP3 inflammasome activation. With this dual function, DDX3X regulates a live-or-die cell-fate decisions under stress conditions.
AdipoGen Life Sciences provides the key standard inflammasome antibodies used in this study:
Other reagents in the inflammasome field are also available from AdipoGen Life Sciences:
LIT: DDX3X acts as a live-or-die checkpoint in stressed cells by regulating NLRP3 inflammasome: P. Samir, et al.; Nature (Epub ahed of print) (2019)
August 09, 2019
The Inflammasome regulates Hematopoiesis through Cleavage of the Factor GATA1
Inflammasomes are large multimolecular complexes involved in innate immune and inflammatory responses. A recent study published by the lab of Prof. Victoriano Mulero (Universidad de Murcia, Spain) describes a new function of the inflammasome as a regulator of the balance between erythroid and myeloid differentiation during hematopoiesis. Activation of the inflammasome and caspase-1 results in the cleavage of the master erythroid transcription factor GATA1, with a decrease in erythrocyte differentiation and in the increase of myeloid cell differentiation.
AdipoGen Life Sciences provides key standard inflammasome research reagents, including Antibodies and Small Molecules. Numerous scientific publications document the quality of our products.
LIT: Inflammasome regulates hematopoiesis through cleavage of the master erythroid transcription factor GATA1: S.D. Tyrkalska, et al.; Immunity 51, 50 (2019)
July 05, 2019
OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin
Asprosin is a fasting-induced hormone that increases plasma glucose levels in the liver. It also stimulates appetite in the hypothalamus by activating the cAMP signaling pathway via an unknown G protein-coupled receptor (GPCR). In a recent study, the lab of Yiguo Wang (Tsinghua University, 100084 Beijing, China) identifies the multipass G protein-coupled receptor olfactory receptor OLFR734, as the Asprosin receptor in liver. The Asprosin-OLFR734 axis plays a key role in hepatic glucose homeostasis during fasting and in obesity.
AdipoGen Life Sciences provides a recombinant protein, monoclonal antibodies and a detection set to study Asprosin.
LIT: OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin: E. Li, et al.; Cell Metabolism 30, 1 (2019)
June 20, 2019
Extracellular Vesicles Containing eNAMPT Extend Lifespan
A recent study published in Cell Metabolism by the lab of Shin-Ichiro Ima (Washington University School of Medicine) shows that the circulating levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a key NAD+ biosynthetic enzyme in mammals, decline with age in mice and humans. When overexpressed eNAMPT increases NAD+ levels in multiple tissues, enhances their function and extends lifespan of mice. The majority of eNAMPT found in serum/plasma circulates in extracellular vesicles (EVs) and it is a necessity for eNAMPT to be in EVs to act on target cells. Detection of eNAMPT in this study is performed by western blotting using Adipogen Life Sciences’ monoclonal antibody anti-Nampt (Visfatin/PBEF), mAb (OMNI379) (Prod. No. AG-20A-0034).
AdipoGen Life Sciences provides best reagents to study NAMPT in vitro and in vivo in human or mouse:
LIT: Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice: M. Yoshida, et al.; Cell Metabol. (ePub ahead of print) (2019)
March 03, 2019
Fibrinogen-like Protein 1 (FGL1) - A Major Ligand of LAG-3
LAG-3 is a coinhibitory immune checkpoint receptor that inhibits T cell response by binding to MHC-II. In a recent study published in Cell, the lab of Prof Lieping Chen (Yale University, US) identifies Fibrinogen-like protein 1 (FGL1), a molecule secreted by the liver and pancreas, as a major ligand for LAG-3 in both human and mouse. FGL1 binding to LAG-3 inhibits T cell response. FGL1 is upregulated in human cancers and high plasma FGL1 is associated with poor clinical outcomes in patients treated with anti-PD1 therapy.
AdipoGen Life Sciences provides a panel of reagents to study this new protein FGL1:
LIT: Fibrinogen-like Protein 1 Is a Major Immune Inhibitory Ligand of LAG-3: J. Wang, et al.; Cell 176, 334 (2019)
February 15, 2019
Protective Role of Irisin in Alzheimer’s Disease
Irisin is a protein cleaved from fibronectin type III domain-containing protein 5 (FNDC5) and has a beneficial role in adipose tissues, bone and brain. A recent study published in Nature Medicine by the labs of O. Arancio, S.Ferreira & F.G. de Felice (Rio de Janeiro, Brazil, New York, US and Kingston, Canada, respectively) showed that FNDC5/Irisin levels are reduced in Alzheimer’s Disease (AD) cerebrospinal fluid in human and mouse and that beneficial effects of exercise on synaptic plasticity and memory in AD models are mediated by FNDC5/Irisin. Addition of AdipoGen Life Sciences' recombinant Irisin (Prod. No. AG-40B-0136) in a mice model of AD was neuroprotective and rescued Amyloid-β oligomer-induced memory impairment.
AdipoGen Life Sciences provides the best recombinant Irisin/FNDC5 proteins, antibody and ELISA kit to study Irisin and FNDC5 in vitro and in vivo:
LIT: Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models: M.V. Lourenko, et al.; Nat. Med. 25, 165 (2019)
January 14, 2019
Manganese (Mn2+) as a New Activator of the NLRP3 Inflammasome in the Brain
Inflammasomes are implicated in physiological and pathological inflammation including neurodegenerative disorders such Parkinson or Alzheimer diseases. Divalent manganese (Mn2+) activates chronic inflammation leading to increase of neurotoxicity. Recently, the lab of A.G. Kanthasamy (Iowa State University, US) showed that Mn2+ activates the inflammasome protein NLRP3 through mitochondrial dysfunction in microglial cells, consequently promoting neuroinflammation. Interestingly, it was observed in the same study that Mn2+ stimulates the release of the adaptor protein ASC in exosomes that can propagate inflammasome activation in neighboring cells.
Following standard inflammasome antibodies from AdipoGen Life Sciences are used in this study in western blot and immunocytochemistry applications:
LIT: Manganese activates NLRP3 inflammasome signaling and propagates exosomal release of ASC in microglial cells: S. Sarkar, et al.; Science Signal. 12, 563 (2019)
December 21, 2018
Irisin - New Receptor Found
Irisin, a protein cleaved from fibronectin type III domain-containing protein 5 (FNDC5), has a beneficial role in adipose tissues, brain and bone. In a recent study, the lab of Bruce Spiegelman (Dana-Farber Cancer Institute, Boston) identified the Irisin receptor on bone and fat cells. Irisin mediates its effect via a subset of αV integrin receptors on osteocytes and adipose cells to produce sclerostin, a local modulator of bone remodeling.
AdipoGen Life Sciences provides the best panel of recombinant Irisin proteins (tagged and untagged), antibody and ELISA Kit for in vitro and in vivo studies:
LIT: Irisin mediates effects on bone and fat via αV integrin receptors: H. Kim, et al.; Cell 175, p1756 (2018)
December 12, 2018
TNF-α - New Function as Potent Growth Factor for Primary Hepatocytes
Supply of cells for regenerative therapies is dependent on the capacity to stably expand healthy primary cells in vitro. However, most adult primary cell types are refractory to in vitro expansion.
A recent study from the lab of Roel Nusse at Standford University shows a key role of the inflammatory cytokine TNF-α in the establishment of long-term 3D mouse organoid cultures from hepatocytes that are able to successfully engraft and repopulate damaged mouse livers. By using a medium for hepatocytes expansion containing the GSK3 inhibitor CHIR99021 (Wnt activator), Growth factor (GF) and Hepatocyte Growth Factor (HGF), they observed that addition of TNF-α (100ng/ml) promotes long-term culture of primary mouse hepatocytes.
AdipoGen Life Sciences manufactures a panel of highly active TNF-α (human) and (mouse) recombinant proteins:
LIT: Inflammatory cytokine TNFα promotes the long-term expansion of primary hepatocytes in 3D culture: W.C. Peng, et al.; Cell 175, 1607 (2018)
November 16, 2018
LAG-3 - A Selective Immune Checkpoint
LAG-3 is an immune checkpoint receptor that inhibits T cell response and cytokines secretion. Similar to CD4, LAG-3 binds to major histocompatibility complex-II (MHC-II) on antigen presenting cells (APCs). A new study from the lab of Taku Okazaki (Tokushima University, Japan) reveals how LAG-3 inhibits the activation of T cell response: it does not recognize MHC class II universally as previously thought, but instead recognizes selectively MHC class II proteins presenting only stably bound peptides. In addition, the same study shows that LAG does not compete CD4 for MHC-II interaction, but it blocks T cells by transducing inhibitory signals via its intracellular region. This recent study gives a new view on LAG-3 that might function more selectively than previously thought and probably acts to maintain immune tolerance to dominant autoantigens.
AdipoGen Life Sciences provides the best standard reagents to study LAG-3 in vitro and in vivo:
LIT: LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII: T. Maruhashi, et al.; Nat. Immunol. 19, 1415 (2018)
October 25, 2018
Arzanol - A NEW Brain Glycogen Phosphorylase (bGP) Agonist
Arzanol is a prenylated heterodimeric phloroglucinyl α-pyrone, isolated from Helichrysum italicum L., a plant of perfumery relevance and used in herbal medicine. This anti-inflammatory compound has a broad polypharmacological profile, shows antioxidant activity in vitro and in vivo, inhibits NF-κB activation as well as HIV-1 replication in T cells, and inhibits critical enzymes of the inflammatory cascade (PGES-1, 5-LOX and COX-1), consequently modulating the release of pro-inflammatory mediators (interleukins, TNFα, and PGE2).
In a recent study, F. del Gaudio, et al. showed by using MS-based chemical proteomics, that arzanol is a high affinity agonist of brain glycogen phosphorylase (bGP). Arzanol directly interacts with bGP, competing for the same allosteric binding site on bGP like AMP (but with higher affinity), inducing similar conformational changes and promoting the transition to the active form, consequently leading to increased bGP enzyme activity. GPs are key enzymes in glycogen metabolism, promoting the rate-limiting step of its mobilization. In brain, glycogen acts as an emergency glucose storage to protect neurons against hypoglycemia and hypoxic stress, being critical for high cognitive processes such as learning and memory consolidation. Since reduced glycogen breakdown is associated with impaired cognitive functions and neuro-degeneration, the activation of glycogen breakdown might be a new therapeutic strategy.
AdipoGen Life Sciences produces high purity Arzanol (Prod. No. AG-CN2-0500).
LIT: Chemoproteomic fishing identifies arzanol as a positive modulator of brain glycogen phosphorylase: F. del Gaudio, et al.; Chem. Commun. 54, 12863 (2018)
February 24, 2018
BAFF and APRIL Inhibitors to study Mice Autoimmunity
The TNF superfamily ligands, BAFF and APRIL, are involved in the pathogenesis of a number of autoimmune diseases by regulating plasma cell survival. AdipoGen Life Sciences provides unique antibodies to study autoimmune diseases in mice by blockade of mouse BAFF or APRIL, such as anti-BAFF (mouse), mAb (blocking) (Sandy-2) or anti-APRIL (mouse), mAb (rec.) (blocking) (Apry-1-1).
In a recent study, Haselmayer et al., tested several inhibitors of BAFF or APRIL in a model of mouse autoimmune disease (SLE) to confirm that inhibition of mouse BAFF and APRIL by the receptor TACI-Fc is more efficient than inhibition of BAFF alone or APRIL alone on long-lived plasma cell survival. To block mouse APRIL in this study, anti-APRIL (mouse), mAb (rec.) (blocking) (Apry-1-1) (Prod. No. AG-27B-0001PF) from AdipoGen Life Sciences was injected in C57BL/6 mice.
LIT: A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells: P. Haselmayer, et al.; Eur. J. Immunol. 47, 1075 (2017)