Recombinant human IL-4 protein

Summary

• High purity human protein (Uniprot number: P05112)
• >98%, by SDS-PAGE quantitative densitometry
• Source: Expressed in E. coli
• 15.1 kDa monomer
• Animal origin-free (AOF) and carrier protein-free
• Manufactured in Cambridge, UK
• Lyophilized from acetonitrile/TFA
• Resuspend in water at >100 µg/mL, prepare single-use aliquots, add carrier protein if desired, and store frozen at -20°C or -80°C

Featured applications

• Stimulation of activated B cell proliferation
• Stimulation of activated T cell proliferation
• Differentiation of B cells into plasma cells
• Adaptive immunity regulator
• Antibody regulation
• Lymphoid differentiation

Bioactivity

Purity

Qkine IL-4 is as biologically active as a comparable alternative supplier protein

Stimulation of proliferation of TF-1 cells with Qkine IL-4 (Qk092, green) and alternative supplier IL-4 (Supplier B, black). Cells were treated in triplicate with a serial dilution of IL-4 for 72 hours and proliferation measured using the CellTiter-Glo (Promega) luminescence assay.

Protein background

Interleukin 4 (IL-4) is an important signaling molecule within the immune system, playing multiple roles in orchestrating immune responses and maintaining immune homeostasis. IL-4 is primarily produced by immune cells, including mast cells, T helper 2 (Th2) cells, eosinophils, and basophils, and exerts its effects through interaction with its specific receptor, IL-4Rα and subsequent activation of downstream signaling pathways [1]. IL-4 plays a crucial role in hematopoiesis, the regulation of antibody production, the stimulation of activated B cell and T cell proliferation, and the differentiation of B cells into plasma cells. IL-4 induces the expression of class II MHC molecules on resting B-cells and aids regulation of the low-affinity Fc receptor for IgE (CD23) expression on lymphocytes and monocytes [2].

IL-4 has a compact, globular fold stabilized by three disulfide bonds. IL-4 consists of a characteristic four-alpha helix bundle with a left-handed twist, along with a two-stranded anti-parallel beta-sheet [2-3]. This structural arrangement allows stability to IL-4 and also facilitates its interaction with its receptor, IL-4Rα. The receptor for IL-4, IL-4Rα, exists in three distinct complexes within the body, each playing a crucial role in mediating IL-4 signaling [4]. Type 1 receptors consist of the IL-4Rα subunit coupled with a common gamma chain, while type 2 receptors comprise the IL-4Rα subunit bound to IL-13Rα1. Type 1 receptors specifically bind IL-4, whereas type 2 receptors have the capacity to bind both IL-4 and IL-13, two cytokines with closely related functions. This differential receptor composition allows for nuanced regulation of immune responses depending on the specific ligands present [5].

IL-4 serves as a regulator of immune cell differentiation and activation. It promotes the differentiation of naive T cells into Th2 cells, which are crucial for orchestrating immune responses against extracellular pathogens and for mediating allergic reactions. Additionally, IL-4 stimulates the proliferation and activation of B cells, leading to the production of antibodies and the formation of memory B cells [8]. IL-4 plays a pivotal role in modulating macrophage polarization and the development of an alternative activation phenotype (M2) associated with tissue repair and resolution of inflammation [9].

In the context of disease, dysregulation of IL-4 signaling has been implicated in various immune disorders, including allergies, asthma, and autoimmune diseases. Enhanced IL-4 production or aberrant IL-4 receptor signaling can contribute to the pathogenesis of allergic inflammation and tissue damage. Therapeutic strategies aimed at targeting IL-4 or its receptor have shown promise in treating these conditions by modulating immune responses and dampening inflammation [8-10].

Background references

1. Paul, W. E. Interleukin 4: a prototypic immunoregulatory lymphokine. Blood 77, 1859–1870 (1991).
2. Gadani, S. P., Cronk, J. C., Norris, G. T., & Kipnis, J. IL-4 in the brain: a cytokine to remember. Journal of Immunology 189, 4213–4219 (2012).
3. Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E. The IL-4 receptor: signaling mechanisms and biologic functions. Annual Review of Immunology 17, 701–738 (1999).
4. Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E. The IL-4 receptor: signaling mechanisms and biologic functions. Annual Review of Immunology 17, 701–738 (1999).
5. Finkelman, F. D., & Urban Jr, J. F. The other side of the coin: the protective role of the TH2 cytokines. Journal of Allergy and Clinical Immunology 102, 705–706 (1998).
6. Ul-Haq, Z., Naz, S., & Mesaik, M. A. Interleukin-4 receptor signaling and its binding mechanism: A therapeutic insight from inhibitors tool box. Cytokine & Growth Factor Reviews 32, 3–15 (2016).
7. Gordon, S., & Martinez, F. O. Alternative activation of macrophages: mechanism and functions. Immunity 32, 593–604 (2010).
8. Chatila, T. A. Interleukin-4 receptor signaling pathways in asthma pathogenesis. Trends in Molecular Medicine 10, 493–499 (2004).
9. Bhattarai, P. et al. IL4/STAT6 Signaling Activates Neural Stem Cell Proliferation and Neurogenesis upon Amyloid-β42 Aggregation in Adult Zebrafish Brain. Cell Reports 17, 941–948 (2016).
10. Hershey, G. K. IL-13 receptors and signaling pathways: an evolving web. Journal of Allergy and Clinical Immunology 111, 677–690 (2003).