Production of functional human interleukin 37 using plants
We demonstrate for the first time that a fully bioactive human IL-37, a newly discovered cytokine acting as a fundamental inhibitor of innate immunity, can be recombinantly produced in plant cells.
Interleukin 37 (IL-37), a newly discovered member of the interleukin (IL)-1 family of cytokines, plays a pivotal role in limiting innate inflammation and suppressing acquired immune responses, thus holding high potential for treating a wide array of human inflammatory and autoimmune disorders. In this study, we have developed transgenic plants as a novel expression platform for production of human IL-37 (IL-37). Plant transformation vectors synthesizing various forms of the b isoform of IL-37, including an unprocessed full-length precursor form (proIL-37b), a mature form (matIL-37b) and an IL-37 fusion protein in which IL-37b was fused to soybean agglutinin (SBA-IL-37b), have been constructed and introduced into tobacco plants. The expression of all forms of IL-37b was driven by a strong constitutive 35S promoter. Transgenic tobacco plants were generated with each of these constructs. Depending on the form of IL-37b being produced, the expression level of proIL-37b reached approximately 1% of TSP, while matIL-37b expression was substantially lower (0.01% TSP). Fusion to SBA substantially increased the expression of matIL-37b, with the expression level of fusion protein accounting for 1% of TSP. Functional analysis using a cell-based in vitro assay showed that plant-made matIL-37b and proIL-37b are both biologically active, but plant-made matIL-37b exhibited significantly greater biological activity than proIL-37b. These results demonstrate that plants have great potential of being a green bioreactor for low-cost, large-scale production of biologically active IL-37.
KeywordsHuman IL-37 Cytokine Anti-inflammatory property Plant molecular farming Genetic transformation Recombinant protein Functional characterization
AN was supported by a Graduate Student Scholarship from Saudi Arabia government. This work was supported in part by the London Health Sciences Centre, London, Ontario, Canada.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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