Product Sheet CL0431

Description

BACKGROUND Interleukin-17 (also known as IL-17A) is the signature cytokine produced by CD4+ alpha-beta-TCR+ T helper 17 (Th17) cells and plays important roles in the development of inflammatory diseases. It is also produced by CD8+ alpha-beta T cells, NKT cells, and gamma-delta T cells, plus some non-T cells, including macrophages and neutrophils.1 Although IL-17A is eponymous with the Th17 lineage, these cells also produce IL-17F, IL-21, IL-22, IL-26, which all function in a similar manner to promote inflammation, and in some cases can act cooperatively or synergistically. IL-17A and IL-17F are quite homologous (∼55%) and can form heterodimers (termed IL-17A/F) that appear to be the major isoform of the cytokine in human PBMCs. All three cytokine forms bind to a common receptor complex, but exhibit distinct signaling potencies, with IL-17A>IL-17A/F>IL-17F. IL-17A and IL-17F bind to a multimeric receptor complex composed of at least two subunits, IL-17RA and IL-17RC. These receptors belong to a specific subclass of cytokine receptors with distinct molecular features that distinguish this family from other types of receptors. IL-17A and IL-17F signaling through their receptors is unusual compared to typical adaptive T helper cell cytokines. Rather than activating JAK-STAT pathways, the IL-17-family cytokines activate pro-inflammatory pathways more typical of innate, pro-inflammatory cytokines such as IL-1 or TLR agonists. All these cytokines activate NF-kappa-B, and many also have been shown to induce MAPK signaling and the C/EBP transcription factors. Thus, the net effect of IL-17A signaling is to induce an innate-type inflammatory effector gene expression program that mediates potent inflammation and plays a key role in host defense. Conversely, in conditions of dysregulation, this inflammatory profile can also promote inflammatory pathology in autoimmunity.2

Receptors for IL-17 are expressed ubiquitously, but the key responsive cells tend to be non-immune cells such as epithelial cells, mesenchymal cells (myoblasts, fibroblasts and adipocytes, osteoblasts) and keratinocytes. IL-17 stimulates expression of inflammatory genes, including cytokines (IL-6, G-CSF, OSM, IL-32), chemokines (CXCL1, CXCL2, CXCL5, CCL20) and other inflammatory effectors (iNOS, anti-microbial genes, acute phase response genes). Accordingly, although IL-17A is made by T cells, its downstream signals are similar to those induced by typical “innate” immune receptors such as Toll-like recepor ligands (e.g. LPS) or IL-1beta. Moreover, IL-17A and IL-17F synergize potently with TNFalpha. Thus, IL-17A may act as a “rheostat” for TNFalpha signaling. Interestingly, IL-17A and IL-17F upregulate expression of TNFRII in synoviocytes. IL-17A also cooperates with IL-1beta and IL-22. Therefore, Th17-related cytokines act cooperatively to amplify inflammatory cascades, which is beneficial in host defense but deleterious in many autoimmune settings.3
 
REFERENCES  
1. O’Brien, R.L. et al: Eur. J. Immunol. 39:662-6, 2009
2. Ishigame, H. et al: Immunity 30:108-19, 2009
3. Gaffen, S.L.: Curr Rheumatol Rep. 11: 365–70, 2009 
 
Products are for research use only. They are not intended for human, animal, or diagnostic applications.
(Click to Enlarge) Interleukin-17 (IL-17) Standard Curve: Using the mouse IL-17 ELISA Kit, O.D. data was graphed against IL-17 protein concentration. The TMB reaction was incubated at 37°C for 29 min.

Details

Cat.No.:
CL0431
Target Protein Species:
Mouse
Range:
15.6 pg/ml – 1000 pg/ml
Specificity:
No detectable cross-reactivity
with any other cytokines
Storage:
Store at 4°C. Use within 6 months.
 
ELISA Kits are based on standard sandwich enzyme-linked immunosorbent assay technology. Freshly prepared standards, samples, and solutions are recommended for best results.

Products

Product Size CAT.# Price Quantity
Mouse IL-17 ELISA Kit: Mouse Interleukin-17 ELISA Kit Size: 96 Wells CAT.#: CL0431 Price: $457.00
-+

Resources/Documents