Semiquinone glucoside derivative provides protection against γ-radiation by modulation of immune response in murine model

Abstract

Present study was undertaken to evaluate radioprotective and immunomodulatory activities of a novel semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1 in C57 BL/6 mice. Whole body survival study was performed to evaluate in vivo radioprotective efficacy of SQGD. To observe effect of SQGD on immunostimulation, Circulatory cytokine (i.e., interleukin-2 (IL-2), IFN-γ, IL-10, granulocyte colony stimulating factor (G-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), and macrophage colony stimulating factor (M-CSF) expression was analyzed in serum of irradiated and SQGD treated mice at different time intervals using ELISA assay. Results of the present investigation indicated that SQGD pre-treatment (-2 h) to lethally irradiated mice provide ∼ 83% whole body survival compared with irradiated mice where no survival was observed at 30(th) post irradiation day. Significant (p < 0.05) induction in IL-2 and IFN-γ expression was observed at all tested time intervals with SQGD pre-treated irradiated mice as compared with irradiated mice alone. However, sharp increase in IL-10 expression was observed in irradiated mice which were found to be subsidized in irradiated mice pre-treated with SQGD. Similarly, significant (p < 0.05%) induction in G-CSF, M-CSF and GM-CSF expression was observed in irradiated mice treated with SQGD as compared with irradiated control mice at tested time intervals. In conclusion, SQGD pre-treatment to irradiated mice enhanced expression of IL-12 and IFN-γ while down-regulated IL-10 expression and thus modulates cytoprotective pro-inflammatory TH1 type immune response in irradiated mice. Further, SQGD pre-treatment to irradiated mice accelerate G-CSF, GM-CSF and M-CSF expression suggesting improved haematopoiesis and enhanced cellular immune response in immuno-compromised irradiated mice that may contribute to in vivo radiation protection.

In vitro stimulatory effect of N‐acetyl tryptophan‐glucopyranoside against gamma radiation induced immunosuppression

“…5,11,19,21 Irradiated macrophages showed suppression of IL‐12 levels at all tested time‐points (except 2 hours; Figure E). Moreover, previous reports have indicated that dwindling IL‐12 levels cause declined stimulation of IFN‐γ by Th 1 cells . On the contrary, NATG pretreatment to irradiated cells revealed a significant ( P < .05) upsurge in IL‐12 levels at all tested time‐points (except 2 hours) clearly suggesting a role of NATG in Th 1 immune response stimulation via IL‐12 pathway …”

“…Radiation exposure resulted in significant increase in cellular IL‐10 expression (Figure C) that may lead to immune suppression due to its Th 1 cytokines down regulating activities and macrophage costimulatory molecule expression that caused inhibition of antigen presentation and cytokine secretion activity by macrophages . On the contrary, NATG pre‐treatment proficiently neutralized radiation‐induced upsurge in IL‐10 expression at all tested time‐points (Figure C) and thus, it may contribute to maintain immune response by stimulating Th 1 pathway.…”

“…IL‐17A expression is mainly secreted in vivo by activated T cells in response to inflammation and infections with bacterial and fungal pathogens . It has been reported that radiation suppresses Th 1 immune response via modulation of IL‐2, IFN‐γ, and ΙL‐17A expression from their respective secretory cells, thus, hindering IL‐6, G‐CSF, GM‐CSF cytokines expression and by inhibiting activation of T lymphocytes and NK cells . TNF‐α, a proinflammatory cytokine, promotes inflammation by upregulation of adhesion molecules, boosting production of chemokines, cell migration to infected and inflamed sites, tissue destruction and subsequent altered tissue homeostasis .…”

“…Therefore, they may have sustainable capability against radiation induced oxidative stress. Our previous study suggested that radioresistant bacteria produced secondary metabolites as a shield against radiation‐induced damage and oxidative stress . Formerly, we had isolated and characterized a novel semiquinone glucoside derivative, a remarkable secondary metabolite, from radioresistant bacteria Bacillus sp.…”

“…Formerly, we had isolated and characterized a novel semiquinone glucoside derivative, a remarkable secondary metabolite, from radioresistant bacteria Bacillus sp. INM‐1, which demonstrated immune‐radioprotective properties . Recent findings have displayed radioprotective and immunoprotective capability of another novel secondary metabolite, N ‐acetyl tryptophan glucopyanoside (NATG), purified and characterized from the radioresistant bacterium Bacillus sp.…”