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:

- Fc (human):FGL1 (human) (rec.) (Prod. No. AG-40B-0184)

- Fc (human):FGL1 (mouse) (rec.) (Prod. No. AG-40B-0185)

- LAG-3 (human):Fc (human) (rec.) (Prod. No. AG-40B-0031)

- LAG-3 (mouse):Fc (mouse) (rec.) (Prod. No. AG-40B-0039)

- anti-LAG-3 (human), mAb (AG-IHC103) (Prod. No. AG-20B-6023)

- anti-LAG-3, mAb (blocking) (11E3) (Prod. No. AG-20B-0011)

- anti-LAG-3 (human), mAb (blocking) (17B4) (Prod. No. AG-20B-0012)

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:

- Irisin (rec.) (CHO) (Prod. No. AG-40B-0136)

- Irisin:Fc (human) (rec) (Prod. No. AG-40B-0115) (for in vivo studies)

- Irisin (rec.) (untagged) (E.coli) (Prod. No. AG-40B-0103)

- FNDC5 (rec) (untagged) (Prod. No. AG-40B-0128)

- FNDC5:Fc (human) (rec) (Prod. No. AG-40B-0153)

- anti-Irisin, pAb (IN102) (Prod. No. AG-25B-0027)

- Irisin Competitive ELISA Kit (Prod. No. AG-45A-0046Y)

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:

- anti-Caspase-1 (p20) (mouse), mAb (Casper-1) (Prod. No. AG-20B-0042)

- anti-NLRP3/NALP3, mAb (Cryo-2) (Prod. No. AG-20B-0014)

- anti-Asc, pAb (AL177) (Prod. No. AG-25B-0006)

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:

- Irisin (rec.) (untagged) (E.coli) (Prod. No. AG-40B-0103)

- Irisin:Fc (human) (rec) (Prod. No. AG-40B-0115)

- Irisin (rec.) (CHO) (Prod. No. AG-40B-0136)

- Irisin, pAb (IN102) (Prod. No. AG-25B-0027)

- Irisin Competitive ELISA Kit (Prod. No. AG-45A-0046Y)

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:

- TNF-α, Soluble (human) (rec.) (Prod. No. AG-40B-0006)

- TNF-α (human) (multimeric) (rec.) (Prod. No. AG-40B-0019)

- TNF-α (mouse) (multimeric) (rec.) (Prod. No. AG-40B-0021)

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:

- LAG-3 (human):Fc (human) (rec.) (Prod. No. AG-40B-0031)

- LAG-3 (mouse):Fc (mouse) (rec.) (Prod. No. AG-40B-0039)

- anti-LAG-3 (human), mAb (blocking) (11E3) (Prod. No. AG-20B-0011)

- anti-LAG-3 (human), mAb (blocking) (17B4) (Prod. No. AG-20B-0012)

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)

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