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

Recombinant Mouse IL-6/IL-6R alpha complex (Catalog #9038-SR) inhibits M1 mouse myeloid leukemia cell proliferation. The ED50 for this effect is 2‑12 ng/mL.

• Reactivity: Mu
• Applications: Bioactivity

Recombinant Mouse 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 2‑12 ng/mL.
• Source: Mouse myeloma cell line, NS0-derived mouse IL-6/IL-6R alpha Complex protein
  

  Mouse IL-6R alpha (Leu20-Glu357) Accession # P22272	GGGSGGGSGGGS	Mouse IL-6 (Phe25-Thr211) Accession # P08505
  N-terminus		C-terminus

• Accession #: P22272 (IL-6 R alpha ) & P08505 (IL-6)
• N-terminal Sequence: Leu20 (major), Leu28 (minor)
• 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: 60 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: 70-87 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 200 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 Mouse 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. 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 (1-3). 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, 6). IL-6 induces signaling through a cell surface heterodimeric receptor complex composed of a ligand binding subunit (IL-6R 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 (7). gp130 is also a component of the receptors for CLC, CNTF, CT-1, IL-11, IL-27, LIF, and OSM (8). Soluble forms of IL-6 R alpha are generated by both alternative splicing and proteolytic cleavage (3). 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 (3). 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, 3). 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 (3, 9). Mature mouse IL-6 shares 39% and 85% amino acid (aa) sequence identity with human and rat IL-6, respectively (10-12). Within the extracellular domain, mouse IL-6 R alpha shares 51% and 89% aa sequence identity with human and rat IL-6 R alpha , respectively (13).

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. Hunter, C.A. and S.A. Jones (2015) Nat. Immunol. 16:448.
4. Erta, M. et al. (2012) Int. J. Biol. Sci. 8:1254.
5. Garbers, C. et al. (2012) Cytokine Growth Factor Rev. 23:85.
6. Cerutti, A. et al. (1998) J. Immunol. 160:2145.
7. Murakami, M. et al. (1993) Science 260:1808.
8. Muller-Newen, G. (2003) Sci. STKE 2003:PE40.
9. Mitsuyama, K. et al. (2006) Clin. Exp. Immunol. 143:125.
10. Chiu, C.P. et al. (1988) Proc. Natl. Acad. Sci. USA 85:7099.
11. Simpson, R.J. et al. (1988) Eur. J. Biochem. 176:187.
12. Van Snick, J. et al. (1988) Eur. J. Immunol. 18:193.
13. Sugita, T. et al. (1990) J. Exp. Med. 171:2001.

Publications for IL-6/IL-6R alpha Complex (9038-SR)(6)

Publications using 9038-SR

• SA Müller, MD Shmueli, X Feng, J Tüshaus, N Schumacher, R Clark, BE Smith, A Chi, S Rose-John, ME Kennedy, SF Lichtentha The Alzheimer&#039;s disease-linked protease BACE1 modulates neuronal IL-6 signaling through shedding of the receptor gp130 Molecular Neurodegeneration, 2023-02-21;18(1):13. 2023-02-21 [PMID: 36810097] (Bioassay, Mouse)
• MB Lutz, S Ali, C Audiger, SE Autenrieth, L Berod, V Bigley, L Cyran, M Dalod, J Dörrie, D Dudziak, G Flórez-Gra, L Giusiano, GJ Godoy, M Heuer, AB Krug, CHK Lehmann, CT Mayer, SH Naik, S Scheu, G Schreibelt, E Segura, K Seré, T Sparwasser, J Tel, H Xu, M Zenke Guidelines for mouse and human DC generation European Journal of Immunology, 2022-10-27;0(0):. 2022-10-27 [PMID: 36303448] (Cell Culture, Human)
• Chun-Chi Chou, Kuo-Tai Hua, Min-Wei Chen, Chin-Jui Wu, Chun-Hua Hsu, Jann-Tay Wang et al. Discovery and characterization of a monoclonal antibody targeting a conformational epitope of IL-6/IL-6R alpha to inhibit IL-6/ IL-6R alpha /gp130 hexameric signaling complex formation mAbs 2022-12-31 [PMID: 35133941] (Bioassay, Mouse)
• Jinrui Dong, Sivakumar Viswanathan, Eleonora Adami, Sebastian Schafer, Fathima F Kuthubudeen, Anissa A Widjaja et al. The pro-regenerative effects of hyperIL6 in drug-induced liver injury are unexpectedly due to competitive inhibition of IL11 signaling eLife 2021-08-26 [PMID: 34435951] (In vivo assay, Mouse)
• P Innamarato, K Kodumudi, S Asby, B Schachner, M Hall, A Mackay, D Wiener, M Beatty, L Nagle, BC Creelan, AA Sarnaik, S Pilon-Thom Reactive Myelopoiesis Triggered by Lymphodepleting Chemotherapy Limits the Efficacy of Adoptive T Cell Therapy Mol. Ther., 2020-06-24;0(0):. 2020-06-24 [PMID: 32615068] (Bioassay, Mouse)
• E Xu, MMA Pereira, I Karakasili, S Theurich, M Al-Maarri, G Rappl, A Waisman, FT Wunderlich, JC Brüning Temporal and tissue-specific requirements for T-lymphocyte IL-6 signalling in obesity-associated inflammation and insulin resistance Nat Commun, 2017-05-03;8(0):14803. 2017-05-03 [PMID: 28466852] (Bioassay, Mouse)

Bioinformatics

• Gene Symbol: Il6
• Uniprot:
  • P22272 (IL-6 R alpha ) & P08505 (IL-6)()