GliSODin® prevents airway inflammation by inhibiting T-cell differentiation and activation in a mouse model of asthma.

Background: Asthma is a chronic inflammatory airway disease characterized by a prevailing type 2 inflammation, airway hyperresponsiveness, and mucus hypersecretion and is driven by various factors among which oxidative molecules, called reactive oxygen species (ROS), play a major role. Superoxide dismutases (SODs) are enzymes that constitute the first line of defense against ROS. Melon SOD-gliadin, which is known as GliSODin®, is commonly used as a nutritional supplement that has proven antioxidant properties. Objectives: In this study, we evaluated the efficacy and mechanism of action GliSODin® in the treatment of allergic asthma. Methods: House dust mite (HDM)-induced asthmatic mice were orally exposed to GliSODin®, and airway hyperresponsiveness, lung inflammation, in vitro T-cell polarization, in vivo T-cell reactivation, and blood immunoglobulin were investigated. Results: GliSODin® reduced airway hyperresponsiveness, lung innate and adaptive immune response, and HDM-specific IgE production. Coculturing CD4+ T-cell with HDM-sensitized dendritic cells and GliSODin® reduced T-cell polarization into Th2 and Th17 cells. Moreover, adoptively transferred CD4+ T cells from asthmatic mice exhibited a reduced reactivation of Th2 and Th17 cells following stimulation with HDM plus GliSODin®. Conclusion: GliSODin® abrogates asthma features and reduces CD4+ T-cell polarization and reactivation. Taken together, these data suggest that GliSODin® could be used for the management of asthma symptoms.

Intestinal cell targeting of a stable recombinant Cu-Zn SOD from Cucumis melo fused to a gliadin peptide.

The mRNA encoding full length chloroplastic Cu-Zn SOD (superoxide dismutase) of Cucumis melo (Cantaloupe melon) was cloned. This sequence was then used to generate a mature recombinant SOD by deleting the first 64 codons expected to encode a chloroplastic peptide signal. A second hybrid SOD was created by inserting ten codons to encode a gliadin peptide at the N-terminal end of the mature SOD. Taking account of codon bias, both recombinant proteins were successfully expressed and produced in Escherichia coli. Both recombinant SODs display an enzymatic activity of ~5000U mg(-1) and were shown to be stable for at least 4h at 37°C in biological fluids mimicking the conditions of intestinal transit. These recombinant proteins were capable in vitro, albeit at different levels, of reducing ROS-induced-apoptosis of human epithelial cells. They also stimulated production and release in a time-dependent manner of an autologous SOD activity from cells located into jejunum biopsies. Nevertheless, the fused gliadin peptide enable the recombinant Cu-Zn SOD to maintain a sufficiently sustained interaction with the intestinal cells membrane in vivo rather than being eliminated with the flow. According to these observations, the new hybrid Cu-Zn SOD should show promise in applications for managing inflammatory bowel diseases.