Recombinant Human Interleukin-36 gamma (IL36G) (Active)
Description
Mechanism of Action
IL-36γ signals through a heterodimeric receptor complex (IL-1Rrp2/IL-1RAcP), driving pro-inflammatory responses:
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Immune Cell Activation: Induces chemokines (CXCL1, CXCL8, CCL20) and cytokines (IL-6, TNF-α) in macrophages, neutrophils, and epithelial cells .
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Antimicrobial Peptide (AMP) Induction: Upregulates cathelicidin (hCAP18/LL37) and β-defensin 2 (hBD2) in macrophages, restricting Mycobacterium tuberculosis growth .
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Inflammasome Crosstalk: Amplified by IL-1β/IL-18 via caspase-inflammasome activation in a feed-forward loop .
Tuberculosis Host Defense
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AMP Production: IL-36γ stimulation increases CAMP (cathelicidin) and DEFB4 (β-defensin 2) mRNA by 15-fold and 12-fold, respectively, in human macrophages .
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M. tuberculosis Growth Restriction**: IL-36 receptor (IL-36R)-dependent inhibition observed in macrophages (42% reduction vs. controls) .
Viral/Bacterial Lung Infections
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Neutrophil Recruitment: Intratracheal IL-36γ in mice increases BAL neutrophils by 300% and CXCL1 levels by 250% within 4 hours .
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GM-CSF Synergy: Combined IL-36γ + GM-CSF boosts IL36G (4-fold), CXCL1 (10-fold), and IL1B (24-fold) in mouse neutrophils .
Chronic Obstructive Pulmonary Disease (COPD)
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Smoke-Induced Inflammation: IL-36γ amplifies CXCL1 (61% reduction in Il36r−/− mice) and IL-6 (48% reduction) in CS + H1N1-exposed lungs .
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Epithelial Activation: Human lung epithelial cells exposed to IL-36γ show 5-fold increases in CXCL1 and IL36G mRNA .
Psoriasis and Skin Inflammation
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Keratinocyte Activation: Induces CCL20 (5-fold), TNF-α (3-fold), and autocrine IL-36γ expression in human keratinocytes .
Comparative Activity of IL-36 Isoforms
| Feature | IL-36α | IL-36β | IL-36γ |
|---|---|---|---|
| Primary Cell Source | Alveolar epithelium | Bronchial epithelium | Macrophages/fibroblasts |
| M. tuberculosis AMP Induction | Moderate | Low | High |
| Chemokine Induction (CXCL1) | 2-fold | 3-fold | 5-fold |
Therapeutic Potential and Clinical Relevance
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Inflammatory Diseases: Blocking IL-36γ reduces neutrophilic inflammation in COPD (61% BAL neutrophil reduction) and psoriasis models .
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Antimicrobial Therapy: Enhances host defense against intracellular pathogens via AMP upregulation .
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Biomarker Potential: Elevated in COPD exacerbations and tuberculous granulomas .
Research Applications
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In Vitro Models: Used to study macrophage polarization (10–100 ng/mL effective dose) .
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Animal Studies: Administered intratracheally (1–5 µg/mouse) or intraperitoneally to model lung inflammation .
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Drug Screening: IL-36R antagonists (e.g., spesolimab) tested in psoriasis clinical trials .
Challenges and Future Directions
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Species Specificity: Human IL-36γ shares only 53% amino acid identity with murine variants, complicating translational studies .
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In Vivo Dynamics: Role in T-cell priming and vaccine adjuvanticity remains underexplored .
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Therapeutic Targeting: Dual IL-1/IL-36 inhibitors (e.g., IL-1RAcP blockers) show promise but require safety profiling .
Product Specs
Generally, the shelf life of the liquid form is 6 months at -20°C or -80°C. For the lyophilized form, the shelf life is 12 months at -20°C or -80°C.
Target Background
- Serum IL-36γ levels were found to be higher in active systemic lupus erythematosus patients and correlated with disease activity and arthritis. PMID: 29571080
- Cathepsin S was identified as the major IL-36γ-activating protease expressed in epithelial cells. PMID: 28289191
- Enhanced expression of IL-36γ was observed in plasma and bronchoalveolar lavage fluid of patients with acute respiratory distress syndrome due to bacterial pneumonia. PMID: 28176791
- IL-36-mediated IL-6 and CXCL8 production in human lung fibroblasts and bronchial epithelial cells may contribute to pulmonary inflammation, particularly those caused by bacterial or viral infections. PMID: 28869889
- A review focusing on the skin as a target for microbial and viral invasion examines the current understanding of IL-36 (IL-36α, IL-36β, and IL-36γ) functions. One proposed physiological function of the IL-36 family is to counteract microbial immune evasion. [Review] PMID: 28811383
- IL-36γ inhibits differentiation and induces inflammation of keratinocytes via the Wnt signaling pathway in psoriasis. PMID: 28924372
- IL-36γ-stimulated endothelial cells secrete the pro-inflammatory chemokines IL-8, CCL2, and CCL20. PMID: 27673278
- Skin injury increases IL-36γ via the activation of the TLR3-SLUG-VDR axis, and IL-36γ induces REG3A to promote wound healing. PMID: 28774595
- A novel Nrf2-IL-36γ pathway mediates autocrine and paracrine regulation of keratinocyte proliferation. PMID: 27183581
- Researchers demonstrated that Mycobacterium tuberculosis infection of macrophages induces IL-36γ production in a two-stage regulated manner. PMID: 27389350
- IL-36γ, a member of the IL-1 superfamily, is involved in host defense and contributes to pro-inflammatory responses and the development of inflammatory diseases. PMID: 27853811
- IL-36γ is significantly more strongly expressed in the epidermis of patients with psoriasis-based erythroderma compared to other inflammatory skin diseases. PMID: 26524325
- A study revealed that plasma concentrations of IL-36α and IL-36γ are overexpressed in active systemic lupus erythematosus patients, and that IL-36α has a substantial pro-inflammatory effect through regulation of IL-6 and CXCL8 production. PMID: 26516833
- IRF6 is likely to promote inflammation in response to P. gingivalis through its regulation of IL-36γ. PMID: 26819203
- Findings indicate that interleukin (IL)-1β-induced interleukin 36 gamma (IL-36γ) expression is mediated by the activation of transcription factors, NF-κB p65 and AP-1 (c-jun). PMID: 26562662
- IL36G was identified as a strong regulator of skin pathology in both lesional and non-lesional skin samples. PMID: 25897967
- Decreased Langerhans cell responses to IL36G: altered innate immunity in patients with recurrent respiratory papillomatosis. PMID: 24950037
- IL-36γ expression inversely correlated with the progression of human melanoma and lung cancer. PMID: 26321222
- IL-36γ is a valuable biomarker in psoriasis patients, both for diagnostic purposes and for measuring disease activity during the clinical course. PMID: 25525775
- CAMP induces IL-36γ expression, leading to the initiation of skin inflammation and occasional exacerbations of psoriasis. PMID: 25305315
- IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in the skin. PMID: 24829417
- This is the first report of extracellular release of endogenous IL-36γ through pyroptosis, suggesting a function of IL-36γ as an alarmin. PMID: 22318382
- Data presented herein provide further insight into the involvement of T-bet in innate immunity and suggest that IL-36γ, in addition to IFNγ, may contribute to the functions of this transcription factor in immunopathology. PMID: 23095752
- Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36α, IL-36β, and IL-36γ) or antagonist (IL-36Ra) activity. PMID: 21965679
- Regulation and function of the IL-1 family cytokine IL-1F9 in human bronchial epithelial cells. PMID: 20870894
- Expression of IL-1F9 is increased in human plaque psoriasis skin and is overexpressed in a transgenic mouse psoriasis model. PMID: 21242515
- IL-1F6 and IL-1F8, in addition to IL-1F9, activate the pathway leading to NF-κB in an IL-1Rrp2-dependent manner in Jurkat cells. PMID: 14734551
- This is the first report of IL-1 genotype association with the inflammation of skeletal muscle following acute resistance exercise that may potentially affect the adaptations to chronic resistance exercise. PMID: 15331687
- This report demonstrates expression of IL1F9 by bronchial epithelial cells induced by pro-inflammatory stimuli, suggesting a function of this molecule in airway inflammation. PMID: 15701729
