Part:BBa_K5522001

IL18-BPa

Sequence and Features

Assembly Compatibility:

• 10
  COMPATIBLE WITH RFC[10]
• 12
  COMPATIBLE WITH RFC[12]
• 21
  COMPATIBLE WITH RFC[21]
• 23
  COMPATIBLE WITH RFC[23]
• 25
  INCOMPATIBLE WITH RFC[25]

  Illegal NgoMIV site found at 1176
  
• 1000
  COMPATIBLE WITH RFC[1000]

Profile

Name: SUMO-IL18-BPa-Fc

Base Pairs: 1542bp

Origin: Homo sapiens

Properties

The protein encoded by this gene is a proinflammatory cytokine of the IL-1 family, constitutively found as a precursor within the cytoplasm of various cells, including macrophages and keratinocytes. The inactive IL-18 precursor is processed into its active form by caspase-1. This cytokine is capable of stimulating interferon-gamma production and regulating both T helper (Th) 1 and Th2 responses. IL-18 has been implicated in the injury of different organs and potentially fatal conditions characterized by a cytokine storm. In humans, the IL-18 gene is located on chromosome 11. Alternatively spliced transcript variants encoding different isoforms have been found for this gene [1-2].

Usage and Biology

IL-18 has been used in many fields, including cancer research and treatment. IL-18BP is induced in the tumor microenvironment (TME) in response to the upregulation of IFNγ as part of a negative feedback mechanism, making it valuable in developing cancer drugs [3]. Additionally, IL-18 has been studied for its role in diseases such as Alzheimer's [4]. Our project aims to explore the use of IL-18 in treating inflammatory bowel disease (IBD).

In this project, the SUMO modification enhances protein stability, and human IL-18BP has four subtypes: IL-18BPa, IL-18BPb, IL-18BPc, and IL-18BPd. Among them, only IL-18BPa inhibits the biological function of IL-18, making it an ideal candidate drug for blocking IL-18 in treating IBD [4-5]. The Fc modification has been shown in other research to slow the degradation of proteins in vivo. A His tag was added to the C-terminal for protein purification, and codon optimization improves gene expression and translational efficiency within E. coli.

References

1. Piersiala K, Hjalmarsson E, da Silva PFN, Lagebro V, Kolev A, Starkhammar M, Elliot A, Marklund L, Munck-Wikland E, Margolin G, Georén SK, Cardell LO. Regulatory B cells producing IL-10 are increased in human tumor draining lymph nodes. Int J Cancer. 2023 Aug 15;153(4):854-866. doi:10.1002/ijc.34555. Epub 2023 May 5. PMID: 37144812.
2. Liang X, Fan Y. Bidirectional two-sample Mendelian randomization analysis reveals a causal effect of interleukin-18 levels on postherpetic neuralgia risk. Front Immunol. 2023 May 25;14:1183378. doi:10.3389/fimmu.2023.1183378. PMID: 37304287; PMCID: PMC10247971.
3. Menachem A, Alteber Z, Cojocaru G, et al. Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects. Cancer Immunology Research, 2024, OOF1-OF17.
4. Yamanishi K, Hata M, Gamachi N, et al. Molecular Mechanisms of IL18 in Disease. Int J Mol Sci. 2023, 24(24).
5. Ihim, S. A., Abubakar, S. D., Zian, Z., Sasaki, T., Saffarioun, M., Maleknia, S., & Azizi, G. (2022). Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment. Frontiers in Immunology, 13, 919973. doi:10.3389/fimmu.2022.919973.