IL 17 Rat
Description
Molecular Structure and Receptor Interactions
Rat IL-17A is a 15–20 kDa glycosylated protein forming homodimers or heterodimers with IL-17F . Its structure features a conserved cystine knot fold with two intrachain disulfide bonds critical for stability . Key structural comparisons include:
IL-17A binds IL-17RA, inducing conformational changes that enable recruitment of IL-17RC/RD for signal transduction . Structural studies reveal receptor binding destabilizes IL-17A’s N-terminal region, preventing steric clashes with IL-17RA loops .
Role in Immune Response and Homeostasis
IL-17A in rats is primarily secreted by Th17 cells, γδ T cells, and innate lymphocytes . Its functions include:
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Mucosal Defense: Enhances tight junction integrity and antimicrobial peptide production in epithelial barriers .
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Neutrophil Recruitment: Stimulates CXCL1, CXCL2, and G-CSF to mobilize neutrophils .
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Synergy with Pro-Inflammatory Cytokines: Amplifies TNF-α, IL-6, and IL-1β production in macrophages and fibroblasts .
Acute Lung Injury (ALI)
IL-17A exacerbates LPS-induced ALI via ERK1/2 and NF-κB pathways :
| Parameter | LPS-Induced ALI (24h) | IL-17 Neutralization |
|---|---|---|
| BALF IL-17 (pg/mL) | 450 ± 35 | 120 ± 20 |
| Neutrophil Infiltration | Severe | Reduced |
| Lung Edema (W/D Ratio) | 5.2 ± 0.3 | 3.8 ± 0.2 |
Neutralizing IL-17A antibodies reduced pulmonary edema and TNF-α/IL-6 levels by 60–70% .
Neuroinflammation and Autism Spectrum Disorder (ASD)
Elevated IL-17A correlates with ASD-like behaviors in rodent models :
IL-17A overexpression in BTBR mice exacerbated social deficits, while IL-17 inhibition improved outcomes .
Autoimmune Arthritis
IL-17A is critical for T cell-driven arthritis in IL-1Ra-deficient rats :
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IL-17⁻/⁻ × IL-1Ra⁻/⁻ Mice: 100% suppression of arthritis incidence vs. 80% in IL-1Ra⁻/⁻ controls .
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Mechanism: IL-17A amplifies IL-1 signaling, driving synovial fibroblast activation and osteoclastogenesis .
Antibody-Based Neutralization
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Anti-IL-17 mAb: Reduced lung MPO activity by 55% and serum IL-6 by 40% in trauma models .
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IL-17RA Blockade: Attenuated ERK1/2 phosphorylation in LPS-challenged rats .
Challenges
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Dual Role: IL-17A is protective against Candida but pathogenic in autoimmune contexts .
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Redundancy: IL-17F compensates for IL-17A in some inflammatory pathways .
Future Directions
Product Specs
Q&A
What experimental designs are recommended for studying IL-17 signaling in rat disease models?
The gold standard involves four-group designs comparing wildtype, saline control, disease-induced, and IL-17 intervention cohorts. For example, OME studies used WT (no treatment), CTRL (sensitization without challenge), OME+Saline, and OME+IL-17 mAb groups . Key parameters include:
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Timing: Sacrifice at standardized endpoints (e.g., day 17 post-challenge)
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Outcome measures: Cytokine quantification in serum (ELISA), middle ear lavage analysis, and histological scoring .
How should IL-17 levels be quantified in rat biological samples?
Three validated methods dominate:
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ELISA: CUSABIO kits with anti-rat IL-17 antibodies, TMB substrate, and OD450 nm measurement
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Multiplex bead immunoassays: Used in ASD models for simultaneous cytokine profiling
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Flow cytometry: Intracellular staining of splenocytes (e.g., 54.8% IFN-γ+/29.4% IL-17+ T cells in uveitis models) .
Critical step: Centrifuge serum at 3000 × g for 10 min at 4°C to prevent degradation .
What are common confounding factors in IL-17 rat studies?
A systematic review of 28 preclinical studies identified:
How to resolve contradictory findings about IL-17's pro- vs anti-inflammatory roles?
The duality arises from model-specific context:
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Pro-inflammatory: In OME, IL-17 activates Notch signaling (p<0.05 vs controls)
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Anti-inflammatory: In autoimmune uveitis, IL-17 reduces IFN-γ+ T cells by 47% (28.9% vs 54.8% in controls) .
Methodological solution: Perform dose-response studies (e.g., 0.05–20 mg/kg IL-17 ) and compare immune cell subtypes across tissues (spleen vs CNS).
What validation strategies confirm IL-17 pathway involvement?
Combine three approaches:
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Neutralization: Anti-IL-17 mAb reduces OME severity scores by 62%
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Pathway inhibition: Notch blockers (e.g., DAPT) suppress IL-17-induced inflammation without altering IL-17 expression .
What quality controls ensure reliable IL-17 data?
Follow CAMARADES criteria:
| Parameter | Compliance Rate |
|---|---|
| Peer review | 100% (28/28 studies) |
| Random allocation | 11% (3/28 studies) |
| Blinded assessment | 32% (9/28 studies) |
| Recommendation: Use SYRCLE's risk-of-bias tool during study design . |
How to address variability in IL-17 measurements across labs?
Standardize using:
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Reference materials: Spike recovery tests (85–115% acceptance)
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Cross-validation: Compare ELISA (CUSABIO) vs Luminex (Milliplex) in split samples
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Kinetic analysis: Collect serial measurements (e.g., P1–P30 in ASD models) .
When should IL-17 data be normalized to disease severity scores?
Apply normalization when:
How to reconcile IL-17 increases in serum vs tissue-specific decreases?
Analyze spatial distribution:
| Compartment | IL-17 Change | Model |
|---|---|---|
| Serum | +158% | OME |
| Cerebellum | -37% | ASD (P30) |
| Mechanism: Blood-brain barrier efflux transporters differentially regulate IL-17 . |
Table 1: IL-17 Alterations Across Rat Models
| Model | IL-17 Change | p-value | Assay |
|---|---|---|---|
| OME | +2.8-fold | <0.001 | ELISA |
| Autoimmune uveitis | -41% | 0.003 | Flow cytometry |
| ASD (MIA) | +1.9-fold | 0.02 | Multiplex |
Table 2: Common Methodological Limitations
Product Science Overview
Interleukin-17 (IL-17) is a family of pro-inflammatory cytokines that play a crucial role in the immune response. The IL-17 family consists of six members: IL-17A, IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F . Among these, IL-17A is the most studied and is often referred to simply as IL-17. IL-17A is produced by a subset of T helper cells known as Th17 cells and is involved in the defense against bacterial and fungal infections .
IL-17A is a potent inducer of inflammatory responses. It promotes the maturation of CD34-positive hematopoietic precursors into neutrophils and stimulates the production of other pro-inflammatory cytokines and chemokines . This cytokine plays a significant role in the pathogenesis of various inflammatory and autoimmune diseases, including rheumatoid arthritis, asthma, multiple sclerosis, psoriasis, and transplant rejection .
Recombinant IL-17 (Rat) is a laboratory-produced version of the natural cytokine, designed for research purposes. It is used to study the biological functions of IL-17 in various experimental models. The recombinant protein retains the biological activity of the native cytokine and is used in studies related to inflammation, immune response, and disease pathogenesis .
IL-17A has been identified as a therapeutic target in several diseases due to its role in promoting inflammation. Inhibitors of IL-17A or its receptor (IL-17RA) are being developed and tested for the treatment of autoimmune and inflammatory conditions . Understanding the functions and mechanisms of IL-17A is crucial for developing new therapeutic strategies.
