Synergic benefits of probiotics and selective antioxidants from TCM on cytokine storm-induced protein damages on skin
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Presented by: Lionel Breton
Introduction
Interleukin 6 (IL-6) is a cytokine that mediates a wide range of inflammatory and immune responses. Its expression is elevated in inflammatory or immunodeficient diseases, including psoriasis, rheumatoid arthritis, and AIDS. IL‑6 signaling is involved in coronary artery disease and the global COVID‑19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS‑CoV‑2, and is also associated with smoking or obesity‑classic cardiovascular risk factors which promote inflammatory states.
Probiotics are known to be beneficial for immune functions and for some of them, control of infectious diseases and inflammation. A synbiotic mixture composed of these specific probiotics’ strains associated to antioxidants known to be efficient against both, oxidative and inflammatory events could be relevant to provide a global beneficial effect on early events of cytokins’ induced stress.
Protein damage leading to the formation of carbonyl groups derives from direct oxidation of several amino acid side chains but can also derive through protein adducts formation with lipid peroxidation products and dicarbonyl glycating compounds. Probiotics activities on skin disorders by topical route, can be explained by i) a direct effect at the site of application by enhancing the skins natural defense barriers and ii) the production of antimicrobial peptides that benefit cutaneous immune responses and eliminate pathogens as commensal strains.
Methods
Human dermal fibroblasts were cultured in calcium-free DMEM, with 2% SVF, at 37 °C and humid atmosphere, supplemented with 5% CO2. Cells were plated (20.000 cells/well) at Day 0 (D0) in 96 well plates containing culture medium and distributed in several experimental groups, containing 6 replicates per group (n=6). The experimental groups were incubated for 24 hours with the synbiotic mixture, in presence of IL-6 (8 ng/mL). The Stress group received only the treatment with IL-6 (8 ng/mL), while the Control group was untreated. Dexamethasone (1μM) has been used as reference. The fluorescence emission was detected and recorded using a fluorescence plate reader. Data management and statistical analyses were accomplished using GraphPad Software.
Results
In this study, a significant increase in oxidized proteins was observed after IL-6 treatment of human dermal fibroblasts. A protection value (%) was obtained considering control group at maximum efficiency (100%) and the stress group at minimum efficiency (at 0%). The symbiotic mix shows a significant protective effect against IL-6-induced protein oxidation: 89% at 200 μg/mL and 100% of protection when applied on cells at 50 μg/mL. In these experimental conditions, dexamethasone (1uM) showed 80% of efficacy.
Discussion and Conclusion
In this study, we have evidenced the ability of selected probiotics strains known for their antiviral and anti-inflammatory profiles in association with antioxidants from TCM, to prevent oxidative proteome damage on human fibroblasts upon cytokins’ stress.
In addition, our model provides relevant early targets in early event of infectious disease and associated inflammation in the skin.
.
Interleukin 6 (IL-6) is a cytokine that mediates a wide range of inflammatory and immune responses. Its expression is elevated in inflammatory or immunodeficient diseases, including psoriasis, rheumatoid arthritis, and AIDS. IL‑6 signaling is involved in coronary artery disease and the global COVID‑19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS‑CoV‑2, and is also associated with smoking or obesity‑classic cardiovascular risk factors which promote inflammatory states.
Probiotics are known to be beneficial for immune functions and for some of them, control of infectious diseases and inflammation. A synbiotic mixture composed of these specific probiotics’ strains associated to antioxidants known to be efficient against both, oxidative and inflammatory events could be relevant to provide a global beneficial effect on early events of cytokins’ induced stress.
Protein damage leading to the formation of carbonyl groups derives from direct oxidation of several amino acid side chains but can also derive through protein adducts formation with lipid peroxidation products and dicarbonyl glycating compounds. Probiotics activities on skin disorders by topical route, can be explained by i) a direct effect at the site of application by enhancing the skins natural defense barriers and ii) the production of antimicrobial peptides that benefit cutaneous immune responses and eliminate pathogens as commensal strains.
Methods
Human dermal fibroblasts were cultured in calcium-free DMEM, with 2% SVF, at 37 °C and humid atmosphere, supplemented with 5% CO2. Cells were plated (20.000 cells/well) at Day 0 (D0) in 96 well plates containing culture medium and distributed in several experimental groups, containing 6 replicates per group (n=6). The experimental groups were incubated for 24 hours with the synbiotic mixture, in presence of IL-6 (8 ng/mL). The Stress group received only the treatment with IL-6 (8 ng/mL), while the Control group was untreated. Dexamethasone (1μM) has been used as reference. The fluorescence emission was detected and recorded using a fluorescence plate reader. Data management and statistical analyses were accomplished using GraphPad Software.
Results
In this study, a significant increase in oxidized proteins was observed after IL-6 treatment of human dermal fibroblasts. A protection value (%) was obtained considering control group at maximum efficiency (100%) and the stress group at minimum efficiency (at 0%). The symbiotic mix shows a significant protective effect against IL-6-induced protein oxidation: 89% at 200 μg/mL and 100% of protection when applied on cells at 50 μg/mL. In these experimental conditions, dexamethasone (1uM) showed 80% of efficacy.
Discussion and Conclusion
In this study, we have evidenced the ability of selected probiotics strains known for their antiviral and anti-inflammatory profiles in association with antioxidants from TCM, to prevent oxidative proteome damage on human fibroblasts upon cytokins’ stress.
In addition, our model provides relevant early targets in early event of infectious disease and associated inflammation in the skin.
.