IL36G Human His
Description
Molecular Structure and Properties
IL36G Human His is a non-glycosylated polypeptide chain containing 192 amino acids (1–169) with a His-tag fusion at the N-terminus. Key structural and biochemical features include:
The His-tag facilitates nickel-affinity chromatography purification, ensuring high purity (>90% as per SDS-PAGE) .
Biological Function and Signaling Pathways
IL36G Human His activates inflammatory pathways via the IL-36 receptor (IL-36R) and IL-1 receptor accessory protein (IL-1RAcP) complex. Key functions include:
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Inflammation Amplification: Drives NF-κB and MAPK signaling, promoting cytokine production (e.g., IL-6, CXCL1) and recruitment of immune cells .
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Th1/Th9 Cell Polarization: Inhibits regulatory T-cell differentiation and enhances Th9 cell responses by upregulating IL-9 and IL-18 .
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Neutrophil-Mediated Pathways: Activated by neutrophil-derived proteases (e.g., cathepsin S, elastase) and induces IL-36γ expression in neutrophils during bacterial/viral infections .
Inflammatory Disorders
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Psoriasis and Skin Inflammation: Elevated IL-36γ levels correlate with psoriasis lesions; IL-36R blockade reduces disease severity .
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Chronic Lung Inflammation: Drives neutrophilic influx in COPD and exacerbates tissue damage during viral infections (e.g., H1N1) .
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Gut Inflammation: Dual role in colitis—pro-inflammatory in chronic states but protective during acute wound healing .
Cancer and Immunotherapy
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Antitumor Activity: Enhances IFN-γ production by CD8+ T cells and NK cells, promoting tumor eradication .
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Cachexia: IL36G-producing monocytes with neutrophil-like features contribute to muscle wasting in cancer-related cachexia .
Neutrophil-IL36γ Feedback Loop
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Activation: Neutrophil proteases (e.g., cathepsin S) cleave pro-IL-36γ to its active form .
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Upregulation: IL-36γ stimulates IL-36γ expression in macrophages and fibroblasts, creating a feed-forward loop .
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Cytokine Synergy: Cooperates with GM-CSF to enhance IL-1β and CXCL1 production in lung inflammation .
Therapeutic Targeting
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IL-36R Antagonists: Block IL-36 signaling to reduce neutrophilic inflammation without impairing IL-1β-mediated immune defense .
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Cancer Immunotherapy: Combining IL36G with IL-12 or tumor vaccines enhances T-cell activation and antitumor efficacy .
Key Research Findings
Product Specs
Product Science Overview
Interleukin-36 gamma (IL-36γ), also known as IL-1F9, is a member of the interleukin-1 (IL-1) family of cytokines. This family includes several pro-inflammatory cytokines that play crucial roles in the regulation of immune responses. IL-36γ is particularly involved in skin inflammatory responses and has been studied for its role in various inflammatory diseases.
IL-36γ is a protein coding gene that produces a cytokine with a molecular weight of approximately 18-22 kDa . The protein consists of 169 amino acids and does not contain a signal sequence, prosegment, or potential N-linked glycosylation sites . Human IL-36γ shares significant sequence homology with its counterparts in other species, including mouse, rat, bovine, and equine .
Recombinant IL-36γ is produced using recombinant DNA technology, where the gene encoding IL-36γ is inserted into an expression system, such as Escherichia coli, to produce the protein in large quantities . The recombinant protein is often tagged with a His (histidine) tag to facilitate purification and detection. The His tag allows the protein to be purified using affinity chromatography, which exploits the affinity of histidine residues for certain metal ions.
The recombinant IL-36γ (His Tag) protein is typically expressed in Escherichia coli and purified to a high degree of purity (≥95%) with low endotoxin levels (≤0.005 EU/µg) . This makes it suitable for various applications, including mass spectrometry and other biochemical assays .
IL-36γ binds to and signals through the IL-36 receptor (IL-36R), which in turn activates the NF-κB and MAPK signaling pathways in target cells . This signaling cascade leads to the production of various chemokines and cytokines that mediate inflammatory responses. IL-36γ is primarily expressed in epithelial cells and plays a significant role in skin inflammation by acting on keratinocytes, dendritic cells, and T-cells .
In cultured keratinocytes, IL-36γ induces the expression of several chemokines, including CCL3, CCL4, CCL5, CCL2, CCL17, CCL22, CXCL8, and CXCL1 . It also stimulates the expression of pro-inflammatory parameters such as TNF-alpha, S100A7/psoriasin, and inducible nitric oxide synthase (iNOS) .
IL-36γ has been implicated in various inflammatory diseases, particularly those affecting the skin. Dysregulation of IL-36γ signaling can lead to conditions such as psoriasis, where it enhances the Th17/Th23 axis and induces psoriatic-like skin disorders . Genetic mutations in the IL-36 receptor antagonist (IL-36Ra) are associated with generalized pustular psoriasis, a rare but severe skin disease .
Research has shown that anti-IL-36 antibodies can attenuate skin inflammation in mouse models, highlighting the potential therapeutic applications of targeting IL-36γ in inflammatory diseases . Additionally, IL-36γ is expressed in other organs, such as the lungs, intestines, joints, and brain, where it may play roles in local inflammatory responses .
