Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues

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Background/Aims: The hematopoietic system is vulnerable to ionizing radiation and is often severely damaged by radiation. Molecules affecting radioresistance include Toll-like receptor 2. We investigated whether Zymosan-A, a novel TLR2 agonist, can protect the hematopoietic system from radiation-induced damage after total body irradiation. Methods: Mice were exposed to total body radiation after treatment with Zymosan-A or normal saline, and their survival was recorded. Tissue damage was evaluated by hematoxylin–eosin staining. The number of nucleated cells in bone marrow was determined by flow cytometry. Cell viability and apoptosis assay were determined by CCK-8 assay and flow cytometry assay. Enzyme-linked immunosorbent assay was used to detect the level of cytokines. Results: Zymosan-A protected mice from radiation-induced death and prevented radiation-induced hematopoietic system damage. Zymosan-A also promoted cell viability and inhibited cell apoptosis caused by radiation, induced radioprotective effects via TLR2, upregulated IL-6, IL-11, IL-12, and TNF-α in vivo. Conclusion: Zymosan-A can provide protection against radiation-induced hematopoietic system damage by targeting the TLR2 signaling pathway. Thus, Zymosan-A can be potentially effective radioprotectant.

Section: Discussionmentioning

confidence: 88%

“…We then proved that TLR2, TLR4, and TLR9 also play important roles in radioresistance [15-17]. In previous studies, we proved that Pam3CSK4 and HKMT, agonists of TLR2, exhibited significant radioprotective effects on mice [15, 18]. …”

Section: Introductionmentioning

confidence: 92%

Zymosan-a Protects the Hematopoietic System from Radiation-Induced Damage by Targeting TLR2 Signaling Pathway

Cheng

Dong

et al. 2017

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“…Recently, BMMCs have become a focus of research due to their ubiquitous distribution in the connective and vascularized tissues or cavities throughout the body and their critical roles in the regulation in variety of immune processes and many inflammatory diseases [2, 26, 27]. Currently, mast cells are considered to function in a manner that is similar to antigen presenting cells in host defense and homeostasis via the release of cytokines and other mediators that recruit T cells to sites of infection [27, 28].…”

Section: Discussionmentioning

confidence: 99%

“…Currently, mast cells are considered to function in a manner that is similar to antigen presenting cells in host defense and homeostasis via the release of cytokines and other mediators that recruit T cells to sites of infection [27, 28]. According to previous studies, the interaction of ICOS with its sole ligand, ICOSL (also known as B7-related protein-1) triggers key T cell activities, including cytokine production and differentiation into the T follicular helper (Tfh) cell lineage over effector lineages [29-32].…”

Section: Discussionmentioning

confidence: 99%

TNF-α Regulates Mast Cell Functions by Inhibiting Cell Degranulation

Gao

Zhang

et al. 2017

Background/Aims: The aim of this study was to investigate the involvement of inducible co-stimulatory ligand (ICOSL) expression in stimulation of mast cells (MCs) by TNF-α and the ability of TNF-α stimulation of MCs to influence CD4+ T cell differentiation and function. The mechanisms underlying TNF-α stimulation of MCs were also explored. Methods: Mast cells and CD4⁺ T cells were prepared from C57BL/6 mice (aged 6–8 weeks). ICOSL expression by MCs was measured by real-time PCR and flow cytometry, and levels of IL-4, IL-10 and IFN-γ were measured by ELISA. Results: ICOSL expression by MCs was increased by TNF-α stimulation, and resulted in interaction with CD4+ T cells. The IL-4 and IL-10 levels in the co-culture system increased, while IFN-γ levels decreased. Furthermore, CD4+CD25+Foxp3+ T cell proliferation was induced by co-culture with TNF-α-stimulated MCs. The mechanism by which TNF-α stimulated MCs was dependent on the activation of the MAPK signaling pathway. Conclusion: TNF-α upregulated the expression of ICOSL on mast cells via a mechanism that is dependent on MAPK phosphorylation. TNF-α-treated MCs promoted the differentiation of regulatory T cells and induced a shift in cytokine expression from a Th1 to a Th2 profile by up-regulation ICOSL expression and inhibition of MC degranulation. Our study reveals a novel mechanism by which mast cells regulate T cell function.

“…IR induced severe injuries in hematopoietic tissue which may lead to death [15, 16]. G-CSF and IL-6 are critical in hematopoiesis [17-20].…”

Section: Discussionmentioning

confidence: 99%

CpG-Oligodeoxynucleotides Improved Irradiation-Induced Injuries by G-CSF and IL-6 Up-Regulation

Zhang

Dong

Guo

et al. 2017

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Background/Aims: This study investigated the radioprotective properties of three classes of CpG-oligodeoxynucleotides (CpG-ODNs) and the underlying mechanisms. Methods: Mice irradiated at different doses(7Gy or 9Gy) were treated with or without ODNs(50μg via intraperitoneal injection). Assays were performed to determine survival rate and the number of white blood cell in peripheral blood. The levels of granulocyte-colony stimulating factor(G-CSF), interleukin 6(IL-6) and interferon-α (IFN-α) were measured using enzyme-linked immunosorbent assay (ELISA). Results: Survival rate of mice irradiated in 7Gy was increased from 50% to about 100% with ODNs pretreatment. ODNs administration increased the number of WBCs of irradiated mice. G-CSF, IL-6 and IFN-α levels were up-regulated with ODNs treatment. Conclusion: All three classes of ODNs protected mice from irradiation-induced injuries. B-class ODNs exhibited the most potent radioprotective property via the up-regulation of G-CSF and IL-6.