Background/Introduction: Interleukin-4 (IL-4), also known as B cell-stimulatory factor-1, is an approximately 18-20 kDa monomeric cytokine that displays pleiotropic effects during immune responses (1-4). Mouse IL-4 is synthesized as a 140 amino acid (aa) precursor with a 20 aa signal sequence and a 120 aa mature chain. The cytokine contains three potential sites for N-linked glycosylation, three intrachain disulfide bonds, and adopts a bundled four alpha-helix structure (5). Analogous to human, mouse IL-4 has a reported alternative splicing short form. Unlike human, this form is suggested to be very minor in expression and of questionable significance (6). Mature mouse IL-4 shares 43%, and 63% aa sequence identity with human and rat IL-4, respectively. Research has shown that human, mouse, and rat IL-4 are all species-specific in their activities (7-9). IL-4 is expressed by Th2-biased CD4 + T cells, basophils, mast cells, NKT and gammadelta T cells, and eosinophils (1-2, 10). IL-4 is a key player in the type 2 immune response as it promotes T helper type 2 (Th2) differentiation and B cell commitment to the immunoglobulin G1 and immunoglobulin E isotypes (11). IL-4 initiates Th2 differentiation by binding to either a type I or type II receptor complex that contains the IL-4 Ralpha subunit coupled to either the gamma chain or the IL-13Ralpha1, respectively (12). Phosphorylation of the cytoplasmic C-terminal tails by the Janus Kinase (JAK) family of tyrosine kinases results from the heterodimerization of the IL-4 receptor on the cell surface (12). This then leads to the recruitment and phosphorylation of STAT6 (12). Following the phosphorylation of STAT6, conformational changes take place leading to dimerization, nuclear translocation, DNA binding and transcriptional activation of several target genes including the genes for IL-4, IL-5, and IL-13, and the Th2 specific factors GATA3 and c-Maf (12). Functionally, IL-4 promotes cell proliferation and survival, immunoglobulin class switch to IgG 1 and IgE in mouse B cells, priming and chemotaxis of mast cells, eosinophils, and basophils, an acquisition of the Th2 phenotype by naïve CD4 + cells, and the proliferation and activation of epithelial cells (13-16). IL-4 is also a significant cytokine in tumor immunology (17). Researchers found in early mouse experiments that IL-4 exhibited potent anti-tumor ability. The mice rejected IL-4 producing tumors and developed long-lasting anti-tumor immunity (17). This is perhaps due to IL-4's anti-angiogenic effect and/or its ability to activate select CD8 + T cells. Paradoxically, new evidence shows that IL-4 is a tumor-promoting molecule, and thus a cytokine with opposing effects (17). This is possible due to the IL-4 induced upregulation of anti-apoptotic molecules in tumor cells, and the downregulation of cytolytic molecules on CD8 + T cells. In addition, tumor produced IL-4 is also suggested to act on local tumor- associated-macrophages (TAMs), inducing the secretion of cathepsins that promote cell migration (18).
NCBI and Uniprot Product Information
Uniprot Description
Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4.
Research Articles on IL-4
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Product Notes
The Mouse IL-4 il4 (Catalog #AAA9135756) is an ELISA Kit and is intended for research purposes only. The product is available for immediate purchase. The AAA9135756 ELISA Kit recognizes Mouse IL-4. It is sometimes possible for the material contained within the vial of "IL-4, ELISA Kit" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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