IL-13 ELISA Kit, Mouse

BACKGROUND Interleukin-13 (IL-13), like IL-4, is an immunoregulatory cytokine secreted predominantly by Th2 type helper T cells in response to signaling through the T cell antigen receptor and by mast cells and basophils upon cross-linkage of the high-affinity receptor for IgE. IL-13 is also produced by activated eosinophils. It has become evident that IL-13 is a key mediator in the pathogenesis of allergic inflammation. IL-13 has been implicated in airway hypersensitivity and mucus hypersecretion, inflammatory bowel disease, and parasitic nematode expulsion.¹

IL-13 shares many functional properties with IL-4, stemming from the fact that they share a common receptor subunit, the alpha subunit of the IL-4 receptor (IL-4Ralpha). Characterization of IL-13-deficient mice, IL-4-deficient mice, and IL-4 receptor alpha-deficient (IL-4Ralpha(-/-)) mice have demonstrated nonredundant roles for IL-13. IL-13 mediates its effects by interacting with a complex receptor system comprised of IL-4Ralpha and two IL-13 binding proteins, IL-13Ralpha1 and IL-13Ralpha2. IL-13 receptors are expressed on human B cells, basophils, eosinophils, mast cells, endothelial cells, fibroblasts, monocytes, macrophages, respiratory epithelial cells, and smooth muscle cells. However, functional IL-13 receptors have not been demonstrated on human or mouse T cells. Thus unlike IL-4, IL-13 does not appear to be important in the initial differentiation of CD4 T cells into Th2-type cells but rather appears to be important in the effector phase of allergic inflammation. IL-13 sequentially binds to IL-13Ralpha1 and IL-4Ralpha forming a high affinity signaling complex. This receptor complex signals through STAT-6 to stimulate the production of chemokines, cytokines and mucus.² Moreover, IL-13Ralpha2 has a high affinity for IL-13 but is insufficient to render cells responsive to IL-13 even in the presence of IL-4Ralpha. IL-13Ralpha2 has a short cytoplasmic tail that lacks box 1 and box 2 signaling motifs, suggesting that it has no direct signaling ability. Indeed, characterization of IL-13Ralpha2-deficient mice has revealed that IL-13Ralpha2 can downregulate IL-13 responses by sequestering IL-13, although there is evidence that IL-13Ralpha2 may contribute to IL-13-induced TGF-beta1-dependent fibrosis. In mice, IL-13Ralpha2 exists in soluble (s) and membrane (mem) forms, which can both bind to IL-13 and modulate its activity. Furthermore, IL-13Ralpha2 was found to be overexpressed in many tumor cells, thus it is also being targeted in cancer models by novel approaches.³ Given the importance of IL-13 as an effector molecule, regulation at the level of its receptors might be an important mechanism of modulating IL-13 responses and thus propagation of the allergic response. Accordingly, IL-13 is an attractive, novel therapeutic target for pharmacologic intervention in allergic disorders.⁴

 

REFERENCES  

1. Mitchell, J. et al: Curr. Opin. Investig. Drugs 11:527-34, 2010
2. Roy, B. et al: J. Leukoc. Biol. 72:580-9, 2002
3. Joshi, B.H. & Puri, R.K.: Immunotherapy 1:321-7, 2009
4. Martin, P.L. et al: Int J Toxicol. 27:351-8, 2008 
 

 

ELISA Kits are based on standard sandwich enzyme-linked immunosorbent assay technology. Freshly prepared standards, samples, and solutions are recommended for best results.