Recombinant Human IL-6/IL-6R alpha Protein Chimera

• Reactivity: Hu
• Applications: Bioactivity

Recombinant Human IL-6/IL-6R alpha Protein Chimera Summary

• Details of Functionality: Measured by its ability to inhibit M1 mouse myeloid leukemia cell proliferation. The ED₅₀ for this effect is 2.5-12.5 ng/mL.
• Source: Human embryonic kidney cell, HEK293-derived human IL-6/IL-6R alpha Complex protein
  

  Human IL-6R alpha (Leu20-Asp358) Accession # P08887	GGGSGGGSGGGS	Human IL-6 Val30-Met212 Accession # P05231
  N-terminus		C-terminus

• Accession #: P08887 (IL-6 R alpha) & P05231 (IL-6)
• N-terminal Sequence: Leu20 (Human IL-6R alpha)
• Protein/Peptide Type: Recombinant Proteins
• Gene: IL6
• Purity: >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Endotoxin Note: <0.10 EU per 1 μg of the protein by the LAL method.

Applications/Dilutions

• Dilutions:
  • Bioactivity
• Theoretical MW: 59 kDa.
  Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.
• SDS-PAGE: 78-93 kDa, reducing conditions

Packaging, Storage & Formulations

• Storage: Use a manual defrost freezer and avoid repeated freeze-thaw cycles.
  • 12 months from date of receipt, -20 to -70 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, -20 to -70 °C under sterile conditions after reconstitution.
• Buffer: Lyophilized from a 0.2 μm filtered solution in PBS with BSA as a carrier protein.
• Purity: >90%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.
• Reconstitution Instructions: Reconstitute at 500 μg/mL in PBS.

Notes

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Alternate Names for Recombinant Human IL-6/IL-6R alpha Protein Chimera

• IL-6/IL-6R alpha Complex

Background

Interleukin-6 (IL-6) is a pleiotropic, alpha -helical, 22-28 kDa phosphorylated and variably glycosylated cytokine that plays important roles in the acute phase reaction, inflammation, hematopoiesis, bone metabolism, and cancer progression (1-5). Mature human IL-6 is 183 amino acids (aa) in length and shares 39% aa sequence identity with mouse and rat IL-6 (6). Alternative splicing generates several isoforms with internal deletions, some of which exhibit antagonistic properties (7-10). IL-6 induces signaling through a cell surface heterodimeric receptor complex composed of a ligand binding subunit (IL-6 R alpha) and a signal transducing subunit (gp130). IL-6 binds to IL-6 R alpha , triggering IL-6 R alpha association with gp130 and gp130 dimerization (11). gp130 is also a component of the receptors for CLC, CNTF, CT-1, IL-11, IL-27, LIF, and OSM (12). Soluble forms of IL-6 R alpha are generated by both alternative splicing and proteolytic cleavage (5). In a mechanism known as trans-signaling, complexes of soluble IL-6 and IL-6 R alpha elicit responses from gp130-expressing cells that lack cell surface IL-6 R alpha (5). Trans-signaling enables a wider range of cell types to respond to IL-6, as the expression of gp130 is ubiquitous, while that of IL-6 R alpha is predominantly restricted to hepatocytes, monocytes, and resting lymphocytes (2, 5). Soluble splice forms of gp130 block trans-signaling from IL-6/IL-6 R alpha but not from other cytokines that use gp130 as a co-receptor (5, 13). IL-6, along with TNF-alpha and IL-1, drives the acute inflammatory response and the transition from acute inflammation to either acquired immunity or chronic inflammatory disease (1-5). When dysregulated, it contributes to chronic inflammation in obesity, insulin resistance, inflammatory bowel disease, arthritis, sepsis, and atherosclerosis (1, 2, 5). IL-6 can also function as an anti-inflammatory molecule, as in skeletal muscle where it is secreted in response to exercise (2). In addition, it enhances hematopoietic stem cell proliferation and the differentiation of Th17 cells, memory B cells, and plasma cells (1, 14).

1. Mansell, A. and B.J. Jenkins (2013) Cytokine Growth Factor Rev. 24:249.
2. Schuett, H. et al. (2009) Thromb. Haemost. 102:215.
3. Erta, M. et al. (2012) Int. J. Biol. Sci. 8:1254.
4. Garbers, C. et al. (2012) Cytokine Growth Factor Rev. 23:85.
5. Mihara, M. et al. (2012) Clin. Sci. (Lond.) 122:143.
6. Hirano, T. et al. (1986) Nature 324:73.
7. Kestler, D.P. et al. (1995) Blood 86:4559.
8. Kestler, D.P. et al. (1999) Am. J. Hematol. 61:169.
9. Bihl, M.P. et al. (2002) Am. J. Respir. Cell Mol. Biol. 27:48.
10. Alberti, L. et al. (2005) Cancer Res. 65:2.
11. Murakami, M. et al. (1993) Science 260:1808.
12. Muller-Newen, G. (2003) Sci. STKE 2003:PE40.
13. Mitsuyama, K. et al. (2006) Clin. Exp. Immunol. 143:125.
14. Cerutti, A. et al. (1998) J. Immunol. 160:2145.

Publications for IL-6/IL-6R alpha Complex (8954-SR)(6)

Publications using 8954-SR

• K Leng, IVL Rose, H Kim, W Xia, W Romero-Fer, B Rooney, M Koontz, E Li, Y Ao, S Wang, M Krawczyk, J Tcw, A Goate, Y Zhang, EM Ullian, MV Sofroniew, SPJ Fancy, MS Schrag, ES Lippmann, M Kampmann CRISPRi screens in human iPSC-derived astrocytes elucidate regulators of distinct inflammatory reactive states Nature Neuroscience, 2022-10-27;25(11):1528-1542. 2022-10-27 [PMID: 36303069] (Bioassay, Human)
• Z Cai, S Tian, T Klein, L Tu, LW Geenen, T Koudstaal, AE van den Bo, YB de Rijke, IKM Reiss, E Boersma, C van der Le, M Van Faasse, I Kema, DJ Duncker, KA Boomars, K Tran-Lundm, C Guignabert, D Merkus Kynurenine metabolites predict survival in pulmonary arterial hypertension: A role for IL-6/IL-6Ralpha Scientific Reports, 2022-07-19;12(1):12326. 2022-07-19 [PMID: 35853948] (Bioassay, Human)
• G Carbotti, B Dozin, S Martini, C Giordano, F Scordamagl, M Croce, G Filaci, S Ferrini, M Fabbi IL-27 Mediates PD-L1 Expression and Release by Human Mesothelioma Cells Cancers, 2021-08-09;13(16):. 2021-08-09 [PMID: 34439164] (Bioassay, Human)
• J Dong, S Viswanatha, E Adami, BK Singh, SP Chothani, B Ng, WW Lim, J Zhou, M Tripathi, NSJ Ko, SG Shekeran, J Tan, SY Lim, M Wang, PM Lio, PM Yen, S Schafer, SA Cook, AA Widjaja Hepatocyte-specific IL11 cis-signaling drives lipotoxicity and underlies the transition from NAFLD to NASH Nature Communications, 2021-01-04;12(1):66. 2021-01-04 [PMID: 33397952] (Bioassay, Human)
• T Kretschmer, M Schulze-Ed, EM Turnwald, R Janoschek, I Bae-Gartz, P Zentis, M Handwerk, M Wohlfarth, A Schauss, E Hucklenbru, J Dötsch, S Appel Effect of Maternal Obesity in Mice on IL-6 Levels and Placental Endothelial Cell Homeostasis Nutrients, 2020-01-22;12(2):. 2020-01-22 [PMID: 31979004] (Bioassay, Human)
• Ohta R, Sugimura R, Niwa A, Saito M Hemogenic Endothelium Differentiation from Human Pluripotent Stem Cells in A Feeder- and Xeno-free Defined Condition. J Vis Exp, 2019-06-16;0(148):. 2019-06-16 [PMID: 31259914] (Bioassay, Human)

Bioinformatics

• Gene Symbol: IL6
• Uniprot:
  • P08887 (IL-6 R alpha) & P05231 (IL-6)()