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scaricalo in formato PDF - labogen srl

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1. Hornung V. et al., 2006. 5'-Triphosphate RNA is the ligand for RIG-I. Science. 314(5801):994-7. 2. Schlee m. et al., 2009. Recognition of 5' triphosphate by RIG-I helicase requires short blunt<br />

double-stranded RNA as conta<strong>in</strong>ed <strong>in</strong> panhandle of negative-strand virus. Immunity. 17;31(1):25-34. 3. Takaoka A. et al., 2007. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator<br />

of <strong>in</strong>nate immune response. Nature. 448(7152):501-5. 4. Yang P. et al., 2010. The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I <strong>in</strong>terferon via a beta-caten<strong>in</strong>dependent<br />

pathway. Nat Immunol. 11(6):487-94. 5. Jones JW. et al., 2010. Absent <strong>in</strong> melanoma 2 is required for <strong>in</strong>nate immune recognition of Francisella tularensis. PNAS, 107(21):9771-6.<br />

6. Ablasser A. et al., 2009. RIG-I-dependent sens<strong>in</strong>g of poly(dA:dT) through the <strong>in</strong>duction of an RNA polymerase III-transcribed RNA <strong>in</strong>termediate. Nat Immunol. 10(10):1065-72. 7. Gitl<strong>in</strong><br />

L. et al., 2006. Essential role of mda-5 <strong>in</strong> type I IFN responses to polyribo<strong>in</strong>os<strong>in</strong>ic:polyribocytidylic acid and encephelamyocarditis picornavirus. PNAS 103(22):8459-8464. 8. Kato H. et al.,<br />

2005. Cell type-specific <strong>in</strong>volvement of RIG-I <strong>in</strong> antiviral response. Immunity. 23(1):19-28.<br />

Dect<strong>in</strong>-1 Agonists<br />

Curdlan NEW<br />

Curdlan is a high molecular weight l<strong>in</strong>ear polymer consist<strong>in</strong>g of ß-(1 -> 3)-l<strong>in</strong>ked glucose residues. Curdlan is produced as a water-<strong>in</strong>soluble polysaccharide<br />

by the soil bacterium, Alcaligenes faecalis. Curdlan is recognized by the membrane bound Dect<strong>in</strong>-1 receptor lead<strong>in</strong>g to the CARD9-dependent activation of<br />

NF-kB and MAP k<strong>in</strong>ases 1 . Furthermore, Dect<strong>in</strong>-1 signal<strong>in</strong>g activates the NFAT transcription factor. Recent data suggest that Curdlan is also recognized by<br />

the cytosolic NLRP3 <strong>in</strong>flammasome complex which cooperates with Dect<strong>in</strong>-1 result<strong>in</strong>g <strong>in</strong> <strong>in</strong> robust activation of IL-1b–mediated <strong>in</strong>flammatory response 2 .<br />

HKCA (Candida albicans)<br />

HKCA is a heat-killed preparation of Candida albicans. C. albicans is an opportunistic yeast that causes serious <strong>in</strong>fections <strong>in</strong> immunocompromised patients.<br />

Beta-glucans represent 40% of the cell wall of C. albicans. Heat kill<strong>in</strong>g of this yeast result <strong>in</strong> the exposure of the beta-glucans on the surface of the cell wall<br />

and their subsequent recognition by the beta-glucan receptor, dect<strong>in</strong>-1 3 . HKCA derives from the stra<strong>in</strong> ATCC 10231.<br />

HKSC (Saccharomyces cerevisiae)<br />

HKSC is a heat-killed preparation of the yeast Saccharomyces cerevisiae. The cell wall of S. cerevisiae consists ma<strong>in</strong>ly of equal amounts of a-mannans and<br />

b-glucans 4 . Early studies have suggested that the phagocytosis of unopsonized HKSC is mediated by both mannose and b-glucans receptors. However, recent<br />

data show that the b-glucan receptor, dect<strong>in</strong>-1, is the predom<strong>in</strong>ant receptor <strong>in</strong>volved <strong>in</strong> this process 5 .<br />

Zymosan - TLR2 & Dect<strong>in</strong>-1 Agonist<br />

Zymosan, an <strong>in</strong>soluble preparation of yeast cell, activates macrophages via TLR2. TLR2 cooperates with TLR6 and CD14 <strong>in</strong> response to zymosan 6 . Zymosan<br />

is also recognized by Dect<strong>in</strong>-1, a phagocytic receptor expressed on macrophages and dendritic cells, which collaborates with TLR2 and TLR6 enhanc<strong>in</strong>g the<br />

immune responses triggered by the recognition of Zymosan by each receptor 7 .<br />

Zymosan Depleted<br />

Zymosan depleted is a S. cerevisiae cell wall preparation treated with hot alkali to remove all its TLR-stimulat<strong>in</strong>g properties 8 . Zymosan depleted activates<br />

Dect<strong>in</strong>-1 but not TLR2.<br />

1. Goodridge HS, et al., 2009. Beta-glucan recognition by the <strong>in</strong>nate immune system. Immunol Rev. 230(1):38-50. 2. Kankkunen P., 2010. (1,3)-beta-glucans activate both dect<strong>in</strong>-1 and NLRP3<br />

<strong>in</strong>flammasome <strong>in</strong> human macrophages. J Immunol. 184(11):6335-42. 3. Gow NA. et al., 2007. Immune recognition of Candida albicans beta-glucan by dect<strong>in</strong>-1.J Infect Dis. 196(10):1565-71.<br />

4. Giaimis J. et al., 1993. Both mannose and b-glucan receptors are <strong>in</strong>volved <strong>in</strong> phagocytosis of unopsonized, heat-killed Saccharomyces cerevisiae by mur<strong>in</strong>e macrophages. J. Leukoc. Biol., 54:<br />

564-571. 5. Brown GD. et al., 2002. Dect<strong>in</strong>-1 Is A Major ß-Glucan Receptor On Macrophages. J. Exp. Med., 196: 407-412. 6. Oz<strong>in</strong>sky A. et al., 2000. The repertoire for pattern recognition<br />

of pathogens by the <strong>in</strong>nate immune system is def<strong>in</strong>ed by cooperation between toll-like receptors. PNAS. 97(25):13766-71. 7. Gantner BN. et al., 2003. Collaborative <strong>in</strong>duction of <strong>in</strong>flammatory<br />

responses by dect<strong>in</strong>-1 and Toll-like receptor 2. J Exp Med. 197(9):1107-17. 8. Gantner BN. et al., 2003. Collaborative <strong>in</strong>duction of <strong>in</strong>flammatory responses by dect<strong>in</strong>-1 and Toll-like receptor<br />

2. J Exp Med. 197(9):1107-17.<br />

NF-kB Activators<br />

PMA<br />

Phorbol 12-myristate 13-acetate (PMA), also known as 12-O-tetradecanoylphorbol 13-acetate (TPA) is a specific activator of Prote<strong>in</strong> K<strong>in</strong>ase C (PKC) and<br />

hence of NF-kB. PMA is the most commonly used phorbol ester. It is active at nM concentrations. PMA causes an extremely wide range of effects <strong>in</strong> cells<br />

and tissues, and is a very potent mouse sk<strong>in</strong> tumor promoter 1 .<br />

TNF-a<br />

Tumor necrosis factor-alpha (TNF-a) is a cytok<strong>in</strong>e that plays a role <strong>in</strong> a variety of biological processes <strong>in</strong>clud<strong>in</strong>g cell proliferation, differentiation and apoptosis 2 .<br />

It acts by activat<strong>in</strong>g transcription factors such as NF-kB and AP-1. InvivoGen provides a recomb<strong>in</strong>ant human TNF-a produced <strong>in</strong> CHO cells and purified by<br />

aff<strong>in</strong>ity chromatography.<br />

1. Chang MS. et al., 2005. Phorbol 12-myristate 13-acetate upregulates cyclooxygenase-2 expression <strong>in</strong> human pulmonary epithelial cells via Ras, Raf-1, ERK, and NF-kappaB, but not p38<br />

MAPK, pathways. Cell Signal. 17(3):299-310. 2. Leong KG & Karsan A. 2000. Signal<strong>in</strong>g pathways mediated by tumor necrosis factor alpha. Histol Histopathol. 15(4):1303-25. Review.<br />

www.<strong>in</strong>vivogen.com/<strong>in</strong>nate-immunity-pamps<br />

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INNATE IMMUNITY 3

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