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      Korean ginseng extract ameliorates abnormal immune response through the regulation of inflammatory constituents in Sprague Dawley rat subjected to environmental heat stress

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          Abstract

          Background

          Increases in the average global temperature cause heat stress–induced disorders by disrupting homeostasis. Excessive heat stress triggers an imbalance in the immune system; thus protection against heat stress is important to maintain immune homeostasis. Korean ginseng ( Panax ginseng Meyer) has been used as a herbal medicine and displays beneficial biological properties.

          Methods

          We investigated the protective effects of Korean ginseng extracts (KGEs) against heat stress in a rat model. Following acclimatization for 1 week, rats were housed at room temperature for 2 weeks and then exposed to heat stress (40°C/2 h/day) for 4 weeks. Rats were treated with three KGEs from the beginning of the second week to the end of the experiment.

          Results

          Heat stress dramatically increased secretion of inflammatory factors, and this was significantly reduced in the KGE-treated groups. Levels of inflammatory factors such as heat shock protein 70, interleukin 6, inducible nitric oxide synthase, and tumor necrosis factor-alpha were increased in the spleen and muscle upon heat stress. KGEs inhibited these increases by down-regulating heat shock protein 70 and the associated nuclear factor-κB and mitogen-activated protein kinase signaling pathways. Consequently, KGEs suppressed activation of T-cells and B-cells.

          Conclusion

          KGEs suppress the immune response upon heat stress and decrease the production of inflammatory cytokines in muscle and spleen. We suggest that KGEs protect against heat stress by inhibiting inflammation and maintaining immune homeostasis.

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          Most cited references23

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          Hsp70 chaperones: Cellular functions and molecular mechanism

          Abstract. Hsp70 proteins are central components of the cellular network of molecular chaperones and folding catalysts. They assist a large variety of protein folding processes in the cell by transient association of their substrate binding domain with short hydrophobic peptide segments within their substrate proteins. The substrate binding and release cycle is driven by the switching of Hsp70 between the low-affinity ATP bound state and the high-affinity ADP bound state. Thus, ATP binding and hydrolysis are essential in vitro and in vivo for the chaperone activity of Hsp70 proteins. This ATPase cycle is controlled by co-chaperones of the family of J-domain proteins, which target Hsp70s to their substrates, and by nucleotide exchange factors, which determine the lifetime of the Hsp70-substrate complex. Additional co-chaperones fine-tune this chaperone cycle. For specific tasks the Hsp70 cycle is coupled to the action of other chaperones, such as Hsp90 and Hsp100.
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            Points of control in inflammation.

            Inflammation is a complex set of interactions among soluble factors and cells that can arise in any tissue in response to traumatic, infectious, post-ischaemic, toxic or autoimmune injury. The process normally leads to recovery from infection and to healing, However, if targeted destruction and assisted repair are not properly phased, inflammation can lead to persistent tissue damage by leukocytes, lymphocytes or collagen. Inflammation may be considered in terms of its checkpoints, where binary or higher-order signals drive each commitment to escalate, go signals trigger stop signals, and molecules responsible for mediating the inflammatory response also suppress it, depending on timing and context. The non-inflammatory state does not arise passively from an absence of inflammatory stimuli; rather, maintenance of health requires the positive actions of specific gene products to suppress reactions to potentially inflammatory stimuli that do not warrant a full response.
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              Cross-talk in the innate immune system: neutrophils instruct recruitment and activation of dendritic cells during microbial infection.

              Type I inflammatory cytokines are essential for immunity to many microbial pathogens, including Toxoplasma gondii. Dendritic cells (DC) are key to initiating type 1 immunity, but neutrophils are also a source of chemokines and cytokines involved in Th1 response ignition. We found that T. gondii triggered neutrophil synthesis of CC chemokine ligand (CCL)3, CCL4, CCL5, and CCL20, chemokines that were strongly chemotactic for immature DC. Moreover, supernatants obtained from parasite-stimulated polymorphonuclear leukocytes induced DC IL-12(p40) and TNF-alpha production. Parasite-triggered neutrophils also released factors that induced DC CD40 and CD86 up-regulation, and this response was dependent upon parasite-triggered neutrophil TNF-alpha production. In vivo evidence that polymorphonuclear leukocytes exert an important influence on DC activation was obtained by examining splenic DC cytokine production following infection of neutrophil-depleted mice. These animals displayed severely curtailed splenic DC IL-12 and TNF-alpha production, as revealed by ex vivo flow cytometric analysis and in vitro culture assay. Our results reveal a previously unrecognized regulatory role for neutrophils in DC function during microbial infection, and suggest that cross-talk between these cell populations is an important component of the innate immune response to infection.
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                Author and article information

                Contributors
                Journal
                J Ginseng Res
                J Ginseng Res
                Journal of Ginseng Research
                Elsevier
                1226-8453
                2093-4947
                13 February 2018
                April 2019
                13 February 2018
                : 43
                : 2
                : 252-260
                Affiliations
                [1 ]Department of Food Science and Biotechnology, College of Life Science, CHA University, Seongnam, Kyeonggi, Republic of Korea
                [2 ]Central Research Institute, Korean Ginseng Research Co., LTD., Yangpyeong, Republic of Korea
                Author notes
                []Corresponding author. Department of Food Science and Biotechnology, College of Life Science, CHA University, CHA Biocomplex, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Kyonggi-do 13488, Republic of Korea. bylee@ 123456cha.ac.kr
                [☆]

                These authors equally contributed to this work.

                Article
                S1226-8453(17)30355-X
                10.1016/j.jgr.2018.02.003
                6437447
                30976163
                15b81b52-3e05-4347-94b0-9af5d2ba91a2
                © 2018 The Korean Society of Ginseng, Published by Elsevier Korea LLC.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 2 December 2017
                : 23 January 2018
                : 7 February 2018
                Categories
                Research Article

                heat stress,immune response,inflammation,korean ginseng extracts,sprague dawley rats

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