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April 2013 Archive

Posted by Chris on April 4th, 2013  ⟩  0 comments

The interleukin family of cytokines is one of the largest and most studied of all the growth factors. Their roles in disease, the immune system, and immune deficiency have made them superstars of cancer research and AIDS/HIV research, not to mention as possible, critical links in such diverse problems such as heart disease, neurological disorders like Alzheimer’s, arthritis and even Crohn’s disease. Interleukins are involved in processes of cell activation, cell differentiation, proliferation, and cell-to-cell interactions. The expression of interleukins is usually strictly regulated, i.e., the factors are often not secreted constitutively. They are most often synthesized after cell activation as a consequence of a physiological or non-physiological stimulus. There are also some interleukins which are autoregulatory and regulate their own synthesis or the expression of their own receptors.

Gold Bio is excited to now offer three interleukins (IL2, IL3 and IL4), recombinant from both human and murine sequence for your research needs! IL2 was the first of the interleukin family to be identified and characterized in the early 1980’s, though the existence of this family of growth factors was known for a few decades before that. IL2 is necessary for the growth, proliferation, and differentiation of T cells to become 'effector' T cells. IL2 has been shown to be similar to IL15, but IL2 is instrumental in adaptive immunity and the development of the immunological memory, playing an important role in both regulatory T cells (Treg) development and function, whereas IL15 is more important in maintaining a highly specific T cell response.

IL3 is a popular cytokine in use for a variety of cell cultures (i.e. mast cells or basophils) providing the cytokinetic connection between the immune and hematopoietic systems. IL3 is capable of inducing the growth and differentiation of multi-potential hematopoietic stem cells, neutrophils, eosinophils, megakaryocytes, macrophages, lymphoid and erythroid cells. Haig, et al. recently showed a synergistic affect between IL3 and another growth factor, KITLG (sometimes called SCF or Stem Cell Factor), on both bone marrow-derived mast cells (BMMC) and serosal/connective-tissue mast cells (CTMC).

IL4 is most closely associated with IL13 and induces native T helper (Th0) cells to become Th2 cells (which then produce more IL4). They are often produced during allergic responses and promote allergic inflammation by activation signal tranducers. IL4 actions are often “neutralized” by Inferon-gamma (IFN-ɣ), which is made by the Th1 cells. Gilbert, et al., showed that IL4 (as well as IL1) are involved in the response of annulus fibrosus (AF) cells derived from nondegenerative tissue to cyclic tensile strain.

If you have any questions about interleukins or any of our other available growth factors, you can contact us at: techsupport@goldbio.com!

 
 

Mahmud, Shawn A., Luke S. Manlove, and Michael A. Farrar. "Interleukin-2 and STAT5 in regulatory T cell development and function." JAK-STAT 2.1 (2013): 0-1.

Haig, David M., et al. "Effects of stem cell factor (kit-ligand) and interleukin-3 on the growth and serine proteinase expression of rat bone-marrow-derived or serosal mast cells." Blood 83.1 (1994): 72-83.

Reddy, E. Premkumar, et al. "IL-3 signaling and the role of Src kinases, JAKs and STATs: a covert liaison unveiled." Oncogene 19.21 (2000): 2532-2547.

Gilbert, Hamish TJ, et al. "The involvement of interleukin-1 and interleukin-4 in the response of human annulus fibrosus cells to cyclic tensile strain: an altered mechanotransduction pathway with degeneration." Arthritis research & therapy 13.1 (2011): R8.

Category Code: 79101 79108

Posted by Chris on April 11th, 2013  ⟩  0 comments

In the ever-evolving world of growth factors, the Cytokine class can potentially encompass nearly every single growth factor we know. Cytokines are typically small, cell-signaling proteins that are used extensively in intercellular communication. It is a family of regulators, involved in immunomodulation, hormone stimulation, hematopoiesis and embryogenesis. But scientists still disagree exactly how to properly categorize a “cytokine”. As they learn more and more about the world of growth factors vs. classic hormones, the clear-cut distinctions we're used to continue to fade away. Classic protein hormones generally circulate throughout the body in nanomolar concentrations, whereas cytokines typically circulate in the picomolar concentrations but some then magnify up to 1000-fold during trauma or infection. However, cytokines are nearly always produced by nucleated cells, whereas classic hormones are most often secreted from glands, such as the pituitary gland or the pancreas.

Two of the most studied groups of cytokines are interleukins (IL) and Colony Stimulating Factors (CSF). CSF2, often referred to as Granulocyte-Macrophage Colonly Stimulating Factor (GM-CSF), is very closely associated with IL3 and IL5. While there is no significant amino acid sequence homology between the three, they exhibit a number of biological similarities. For instance, they all contain 4 α-helices and their tertiary structures are similar. They are also closely linked on the same chromosome in both human and mice (Chromosome 5 in humans and Chromosome11 in mice). Finally, CSF2 competes with IL3 and IL5 for binding to their respective receptors (Miyajima 1993).

CSF2 has been shown to be an integral signal factor (along with IGF-1, IL1 and activin) produced in the preimplantation development in a number of mammals, including humans, mice, pigs and cows. Treatment with CSF2 in cows during in vitro fertilization was able to significantly reduce pregnancy loss and enhanced embryonic compentence for posttransfer survival (Loureiro 2009). The lack of CSF2 in knockout mice have shown smaller birth size, fetal growth retardation, and increased mortality within the first 3 weeks.

CSF2 has also been tested in a recent phase II trial as an adjuvant treatment for post-pancreatic cancer patients (Lutz 2011). Pancreatic cancer is the 4th leading cause of cancer-related deaths in the US and surgical removal of the pancreas remains the only viable solution to cure it. But the survival rate at 2 years post surgury remains only 42% and 5 years is only 15-20%! Lutz et al. developed an "irradiated CSF2 transfected allogeneic whole cell tumor lines for pancreas ductal adenocarcinoma immunotherapy". Lutz saw promising results over 6 months of post surgical treatment with the immunotherapy and suggested a future, multicenter phase II trial.

CSF3, also known as Granulocyte Colony Stimulating Factor (G-CSF) is a glycoprotein which stimulates bone marrow to produce granulocytes and stem cells and then to release them into the blood stream. CSF3 is commonly produced by immune cells and naturally exists in two forms, a 180 amino acid protein and the more abundant and more active 174 amino acid protein. It has also been recently implicated as being in a class of peripherally circulating peptides which have the ability to alter CNS functions and structure (Diederich, 2009). Diederich showed that CSF3 reduced apoptosis and controled the proliferation and differentiation of neural stem cells and activated several kinases (ERK1, 2 and 5) upstream of CREB (cAMP Response Element-Binding protein), indicating a prominent role in hippocampal function.

We'd love to discuss your particular growth factor needs and any additional growth factors you'd like to see on our website! If you have any questions, just email us at techsupport@goldbio.com.

Miyajima, A., et al. "Receptors for granulocyte-macrophage colony-stimulating factor." Blood 82 (1993): 1960-1974.

Loureiro, Bárbara, et al. "Colony-stimulating factor 2 (CSF-2) improves development and posttransfer survival of bovine embryos produced in vitro." Endocrinology 150.11 (2009): 5046-5054.

Robertson SA, Roberts CT, Farr KL, Dunn AR, Seamark RF. Fertility impairment in granulocyte-macrophage colony-stimulating factor-deficient mice. Biological Reprodution 60 (1999): 251–261

Lutz, Eric, et al. "A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma: a phase II trial of safety, efficacy, and immune activation." Annals of surgery 253.2 (2011): 328.

Diederich, Kai, et al. "Synergetic effects of granulocyte-colony stimulating factor and cognitive training on spatial learning and survival of newborn hippocampal neurons." PloS one 4.4 (2009): e5303.

Category Code:79101 79108

Posted by Chris on April 18th, 2013  ⟩  1 comments

In all of our recent talk about growth factors, let us not forget that, in nature, growth factors are only ever half of the equation. Receptors are proteins which are often found in the plasma membrane of a cell that receive chemical signals (molecular binding) from outside of the cell and direct the cell to do something specific; such as dividing, dying or allowing transmembrane transportation. Typically, growth factor receptors use one of three pathways: JAK/STAT, MAP Kinase or PI3 Kinase.

Nearly all of the 22 Fibroblast Growth Factors (FGFs) that exist in humans bind to one of four FGF Receptors (FGFRs). The FGFRs are single-pass transmembrane receptors which help to tightly regulate the FGF signaling (along with heparan sulfate) by means of their binding specificity. The FGFRs are composed of three immunoglobulin-like (Ig) domains (D1-D3), which are involved in ligand interaction, a single transmembrane helix domain, a string of acidic residues between the first and second Ig domain and an intracellular domain with tyrosine kinase activity (Givol, 1992). Further, the D3 domain may have alternative splicing between its exons (see picture), resulting in two additional isoforms; b and c. The combination of these four basic receptors and their isoforms result in 7 principle FGFRs: FGFR1c, FGFR1b, FGFR2c, FGFR2b, FGFR3c, FGFR3b, and FGFR4.

The FGFRs are capable of binding to more than one FGF, and most FGFs are capable of binding to more than one FGFR (although there is usually a preferred interaction). The alternative splicing of the D3 domain restricts the ligand specificity of FGFR1b-3b to mesenchymally expressed FGFs and that of FGFR1c-3c to epithelially expressed FGFs (Beenken, 2012). Interestingly, FGF1 (or acidic FGF) is the only FGF that appears to have no specific binding preferences, binding equally well with both the “b” and “c” isoforms! Beenken et al., researched into the underlying plasticity of FGF1, and discovered that the N-terminal region was the key determinant of its receptor binding promiscuity (and in fact that the N-terminal region is also the key determinant in most FGF’s specificity) as opposed to the interface of its core and the alternatively spliced βC’-βE and βF-βG loops of the D3 region of the receptor. For a more in-depth read of their fascinating research, you can read it online at The Journal of Biological Chemistry. And if you have any questions about our available growth factors, or any of our products, just email us at techsupport@goldbio.com!
 
 

Givol, D., & Yayon, A. (1992). Complexity of FGF receptors: genetic basis for structural diversity and functional specificity. The FASEB journal, 6(15), 3362-3369.

Beenken, Andrew, et al. (2012). Plasticity in Interactions of Fibroblast Growth Factor 1 (FGF1) N Terminus with FGF Receptors Underlies Promiscuity of FGF1. Journal of Biological Chemistry, 287(5), 3067-3078.

Category Code: 79101 79108

Posted by Chris on April 25th, 2013  ⟩  0 comments

The FGF1 subfamily of Fibroblast Growth Factors was the first of the FGFs to be isolated and identified around 1975 by Gospodarowicz and company. This subfamily is often called the “prototypical” FGF, comprised of 3 coding exons and exon 1 comprising the initiation methionine (Ornitz 2001). Prototypical, however, does not necessarily mean “ancestral”. Itoh and Ornitz (Itoh 2008) described a likely evolutionary tree, starting with an FGF13-like growth factor which eventually evolved into the 22 proteins we have today.

While considered paracrine FGFs, neither FGF1 nor FGF2 are typically secreted by the cell nor do they have N-terminal hydrophobic sequences (Itoh 2011). It is possible that they are released from damaged cells or some other exocytotic mechanism. It has also been reported that these growth factors can be directly translocated to the nucleus and act in an intracine manner (Antoine, 1997). The structure of the FGF1 mRNA is considered to be the least complicated of all the FGFs because not only does is it missing the signal sequence, but the open reading frame is flanked by termination codons. In contrast, FGF2 does not have the flanking codons and instead contains multiple alternative upstream CUG start sites for translation (Jackson, 1992).

The physiological roles of FGF1 and FGF2 are still not clearly understood. Null phenotypic mice are still viable and fertile and appear completely normal (although FGF2 knockout mice tend to have a decreased vascular tone and recover slower from ischaemic heart injury) (Itoh, 2011). FGF1 and FGF2 are involved in the promotion of endothelial cell proliferation as well as the in the organizing of endothelial cells into tube-like structures, promoting blood vessel growth. FGF1 has even been shown in induce angiogenesis in heart tissue in after coronary disease (Stegman, 2000). In addition, FGF1 and FGF2 seem to be involved in the regulation of synaptic plasticity and processes attributed to learning and memory in the hippocampus (Zechel, 2010).

FGF1 is also known to repair nerve injury, enabling functional regeneration of transected spinal cords in rats (Cheng, 1996) and also restored some function to paralyzed limbs of a 6-month old boy suffering from brachial plexus avulsion (Lin, 2005). FGF2 is one of the most potent regulators of human embryonic stem cell (hESC) self renewal and is an essential component of most culture media used to maintain their pleuripotency.

There is a great deal of cross-reactivity between different species of FGF1 or FGF2, with greater than 96% amino acid homology for both growth factors between mice, humans and rats. At Gold Bio, we’re committed to providing you the best source of these recombinant proteins! For more questions about these growth factors or any of our other products, you can email us at techsupport@goldbio.com.
 
 

Ornitz DM. and Itoh, N. (2001). "Fibroblast growth factors". Genome Biol. 2 (3): REVIEWS 3005.

Itoh, N., & Ornitz, D. M. (2008). Functional evolutionary history of the mouse Fgf gene family. Developmental Dynamics, 237(1), 18-27.

Itoh, N., & Ornitz, D. M. (2011). Fibroblast growth factors: from molecular evolution to roles in development, metabolism and disease. Journal of biochemistry, 149(2), 121-130.

Antoine, M., Reimers, K., Dickson, C., and Kiefer, P. (1997) Fibroblast growth factor 3, a protein with dual subcellular localization, is targeted to the nucleus and nucleolus by the concerted action of two nuclear localization signals and a nucleolar retention signal. J. Biol. Chem. 272, 29475_2981

Stegmann, T. J., Hoppert, T., Schneider, A., Gemeinhardt, S., Köcher, M., Ibing, R., & Strupp, G. (2000). Induction of myocardial neoangiogenesis by human growth factors. A new therapeutic approach in coronary heart disease]. Herz, 25(6), 589.

Zechel S, Werner S, Unsicker K, von Bohlen und Halbach O. 2010. Expression and functions of fibroblast growth factor 2 (FGF-2) in hippocampal formation. Neuroscientist 16: 357-373.

Cheng, H., Cao, Y., & Olson, L. (1996). Spinal cord repair in adult paraplegic rats: partial restoration of hind limb function. Science, 273(5274), 510-513.

Lin, P. H., Cheng, H., Huang, W. C., & Chuang, T. Y. (2005). Spinal cord implantation with acidic fibroblast growth factor as a treatment for root avulsion in obstetric brachial plexus palsy. Journal of the Chinese Medical Association, 68(8), 392-396.

Jackson, A., Friedman, S., Zhan, X., Engleka, K. A., Forough, R., & Maciag, T. (1992). Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells. Proceedings of the National Academy of Sciences, 89(22), 10691-10695.

Category Code: 88221 79101

Posted by unknown on April 22nd, 2013  ⟩  0 comments

Today is a great day to do something good for the environment, but we believe that it’s also important to consider how everyday business practices impact the world in which we live. I want to take this Earth Day to point out some of the sustainability initiatives we are taking on here at Goldbio, and show you how they not only reduce our carbon footprint, but they also save money.

GoldBio Sustainability

Ambient Ground Shipping – We ship our products at ambient temperature by default, making items that need to be shipped on ice the exception, rather than the other way around.  Shipping at ambient temperature allows us to skip out on the Styrofoam cooler and blue ice.  Furthermore, we can then ship them via FedEx and UPS ground, eliminating an airplane from the equation.  This drastically reduces the carbon footprint of each shipment, and it also saves our customers more than 80% in shipping costs.

Shipping Materials – Cardboard boxes: made from recycled materials and recyclable. Packing peanuts: made from recycled material and recyclable.  Our standard packing materials are sustainable.  Even though this doesn’t affect your purchase cost, it may help you sleep a little better.

Internal Efforts – Within the office, we also do our part in a number of small ways. This includes recycling everything that can be recycled, reusing old containers and other goods. Using a water fountain to refill cups and bottles, and using real utensils rather than disposable. 

You’ve heard me say many times that we look toward the future with hope, knowing that our products will be used in discovery that benefits all of us. We feel that anything we can do, big or small, to use less will save money and do a little extra for our future.

Category Code: 79105 88261