• Journal of Ginseng Research
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• v.43 no.2
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• pp.252-260
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• 2019

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 ($40^{\circ}C$/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 $factor-{\kappa}B$ 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.

• Animal Bioscience
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• v.36 no.10
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• pp.1604-1611
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• 2023

Objective: The aim of this study was to investigate the protective effect of wheat phytase as a structural decomposer of inflammatory nucleotides, extracellular adenosine triphosphate (ATP), and uridine diphosphate (UDP) on HT-29 cells. Methods: Phosphatase activities of wheat phytase against ATP and UDP was investigated in the presence or absence of inhibitors such as L-phenylalanine and L-homoarginine using a Pi Color Lock gold phosphate detection kit. Viability of HT-29 cells exposed to intact- or dephosphorylated-nucleotides was analyzed with an EZ-CYTOX kit. Secretion levels of pro-inflammatory cytokines (IL-6 and IL-8) in HT-29 cells exposed to substrate treated with or without wheat phytase were measured with enzyme-linked immunosorbent assay kits. Activation of caspase-3 in HT-29 cells treated with intact ATP or dephosphorylated-ATP was investigated using a colorimetric assay kit. Results: Wheat phytase dephosphorylated both nucleotides, ATP and UDP, in a dose-dependent manner. Regardless of the presence or absence of enzyme inhibitors (L-phenylalanine and L-homoarginine), wheat phytase dephosphorylated UDP. Only L-phenylalanine inhibited the dephosphorylation of ATP by wheat phytase. However, the level of inhibition was less than 10%. Wheat phytase significantly enhanced the viability of HT-29 cells against ATP- and UDP-induced cytotoxicity. Interleukin (IL)-8 released from HT-29 cells with nucleotides dephosphorylated by wheat phytase was higher than that released from HT-29 cells with intact nucleotides. Moreover, the release of IL-6 was strongly induced from HT-29 cells with UDP dephosphorylated by wheat phytase. HT-29 cells with ATP degraded by wheat phytase showed significantly (13%) lower activity of caspase-3 than HT-29 cells with intact ATP. Conclusion: Wheat phytase can be a candidate for veterinary medicine to prevent cell death in animals. In this context, wheat phytase beyond its nutritional aspects might be a novel and promising tool for promoting growth and function of intestinal epithelial cells under luminal ATP and UDP surge in the gut.

• IMMUNE NETWORK
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• v.24 no.2
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• pp.14.1-14.26
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• 2024

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4⁺ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8⁺ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8⁺ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4⁺ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.126-131
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• 2008

Immunosuppressive therapy after organ transplantation is routinely used to prevent rejection of the organ, because this decreases the risk of adverse events, infection, and malignancies. Recently, ursodeoxycholic acid (UDCA), which is isolated from the dried bile of adult Chinese bears, has been shown to reduce the incidence and severity of acute rejection of liver allograft during early phase of liver transplantation. Therefore, in this study, we investigated the effect of UDCA on the proliferation of splenocytes exposed to PMA plus ionomycin. Our results demonstrated that UDCA decreased the splenocytes' proliferation in a dose-dependent manner. The decreased cell proliferation was accompanied with the decreased secretion of cytokines such as IL-2, IFN-${\gamma}$ and TNF-${\alpha}$. In addition, the pretreatment of UDCA on splenocytes stimulated with PMA plus ionomycin decreased the mRNA levels of cytokines (IL-2, IFN-${\gamma}$ and TNF-${\alpha}$) and costimulatory molecules (B7.2 and PD-L1). These results suggest the beneficial effect of UDCA on organ transplantation by decreasing lymphocyte proliferation.

• Journal of Society of Preventive Korean Medicine
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• v.16 no.3
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• pp.155-165
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• 2012

Objective : The object of this study is to confirm the immune enhancement effect of Rubus coreanus Miquel (RC) (30% EtOH extract) on RAW264.7 mouse macrophage cell line. Methods : RAW264.7 cells were treated with $10-500{\mu}g/mL$ RC for 24 hours. Cell viability was then measured using WST assays. Levels of intracellular NO and ROS were measured by Griess reagent and DCFH-DA staining respectively. Levels of iNOS and COX-2 mRNA was determined by RT-PCR. Secretion levels of IL-$1{\beta}$ and IL-6 cytokines were evaluated by sandwich ELISA assay. Western blot analysis was performed to measure the levels of intracellular molecules related to MAPKs pathways. Results : RC suppressed the growth of RAW264.7 cells. RC increased the production of NO and ROS. RC increased the mRNA and protein levels of COX-2 and iNOS. RC augmented the levels of secreted IL-$1{\beta}$ and IL-6 cytokines. RC increased MAPKs phosphorylation. Conclusion : In summary, our result shows that RC has inflammatory effect increasing the levels of NO, ROS and secreted cytokines and activating MAPKs. Hence, RC seems to have an immune enhancement effect.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1315-1321
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• 2008

Chan-Su (Venenum bufonis) has long been for a variety of other purposes including treatment of inflammation in the folk medicine recipe. Since nitric oxide (NO) is one of the major inflammatory parameters, we first studied the effects of Chan-Su on NO production in lipopolysaccharide (LPS)-stimulated BV2 microglial cells, Chan-Su inhibited the secretion of NO in BV2 microglial cells, without affecting cell viability, The protein level of inducible nitric oxide synthase (iNOS) was decreased by Chan-Su, And Chan-Su also inhibited production of prostaglandin E2 (PGE2) and expression of cyclooxygenase (COX)-2. Proinflammatory cytokines, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$ and IL-12, were inhibited by Chan-Su in a dose-dependent manner. And Chan-Su inhibited the degradation of ${IkB-\alpha}$, which was considered to be inhibitor of nuclear factor $(NF)-{\kappa}B$, one of a potential transcription factor for the expression of iNOS, COX-2 and proinflammatory cytokines. These results suggest that Chan-Su could exert its anti-inflammatory actions by suppressing the synthesis of NO through inhibition of $I{\kappa}B-{\alpha}$ degradation.

• Journal of Dental Rehabilitation and Applied Science
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• v.37 no.2
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• pp.88-94
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• 2021

Purpose: The purpose of this study was to evaluate the anti-inflammatory effects of non-thermal atmospheric pressure plasma (NTP) on human gingival fibroblasts (HGFs) for clinical application of periodontal treatment. Materials and Methods: HGFs were treated with Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS). Customized NTP device was developed for periodontal in vitro study. Cell viability was evaluated with cell counting kit-8. The levels of inflammatory cytokines, including interleukin (IL)-8 and 6, were determined by enzyme-linked immunosorbent assay. Results: When NTP was applied, the cell viability did not change significantly, and there was no difference for 6 h and 24h. When Pg LPS was treated to HGFs, the secretion of IL-8 and IL-6 was increased compared to the control group. But when the NTP was applied, the secretion of them was significantly decreased. Conclusion: NTP did not affect cell viability of HGFs. And it inhibited the LPS-induced production of IL-8 and IL-6.

• Journal of Life Science
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• v.25 no.1
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• pp.75-83
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• 2015

Curcuma longa L. (CL), a traditional medicinal plant, is well known as a functional food ingredient. The major component of CL is a curcumin of anthocyanin family that has multi-functions such as antimicrobial, anticancer, and antioxidant activity. In this study, fermented milk containing CL was prepared using a mixed strain culture (Bifidobacterium bifidus, Streptococcus thermophilus, Lactobacillus acidophilus), and its physicochemical properties were characterized. In addition, inflammatory cytokine-modulating effects of the fermented milk were also investigated. As regards the properties of fermented milk, the growth rate of lactic acid bacteria in fermented milk containing CL was found to be remarkably more rapid than control. During fermentation, caseins and whey proteins were observed to be partially hydrolyzed, and lactic acid and acetic acid were produced in larger amounts than in the control. The sensory score of fermented milk containing CL was lower than control, owing to its bitter taste and strong flavor. RAW 264.7 cells treated with CL fermented milk supernatant showed no cytotoxicity. Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$) and interleukin-6 (IL-6) were significantly produced by fermented milk with CL, compared to control. The secretion of nitric oxide (NO) from RAW 264.7 cells significantly increased relative to the control. Results from the present study suggested that CL could be used as a natural immunomodulating ingredient for making yogurts, beverages, and other products.

• Korean Journal of Microbiology
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• v.55 no.3
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• pp.213-219
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• 2019

Acne is a chronic inflammatory disease outbreak in the sebaceous glands within the hair follicle. The proliferation of Propionibacterium acnes (P. acnes) causes monocytes to stimulate secretion of inflammatory cytokines. A number of studies proposed the inhibitory effects of P. acnes-mediated inflammation by several natural extracts. However, studies on the effect of Eurya persicifolia Gagnep. (E. persicifolia) extracts on the inflammatory responses by P. acnes have not been explored yet. In this study, we investigated the anti-inflammatory effect of E. persicifolia extract in the inflammatory reactions induced by P. acnes. We found that E. persicifolia extract successfully diminished the expression levels of inflammatory mediators such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and iNOS in P. acnes-activated mouse macrophage RAW 264.7 cells. We found that the immunosuppressive effect of E. persicifolia extract in the P. acnes-activated inflammatory signaling is mediated by the regulation of NF-${\kappa}B$ transcriptional activation, which is a key regulator of inflammatory cytokine expression. Our results suggest that E. persicifolia extract held potentials for the treatment of P. acnes by suppressing NF-${\kappa}B$ signaling pathways.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.26 no.1
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• pp.19-34
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• 2013

Objective : This study was performed to evaluate the effect of immune reaction inductive substances such as PMA, LPS, DPE, DNCB and WP, the whitman pigra extracting substance at simultaneously on the translocation of $NF{\kappa}B$ towards to the nucleus and the mRNA expression patterns of various cytokine genes in THP-1 cells, monocytes of human. Methods : To analyze the cytokine genes expressions, the RT-PCR method was used, and measuring TNF-${\alpha}$ that had been secreted during cell culture by the ELISA method. The morphological changes were observed during THP-1 cell by a scanning electron microscope and the quantitative distribution of $NF{\kappa}B$ in the cell that was analyzed through immunocytochemistry and a confocal microscopy. Results : WP showed different influences onto the mRNA expression patterns of cytokine genes with PMA, LPS. DPE and DNCB according to the types of immune inductive substances in the THP-1 cells. Upon treating PMA and DPE on the THP-1 cells at the same time or either additionally treating WP thereon, the movement of $NF{\kappa}B$ increase towards the nucleus from cell cytoplasm was able to be observed. The expressions of IL-$1{\alpha}$ and IFN-${\gamma}$ induced by PMA and PMA+DNCB were suppressed by WP while the expression of TGF-${\beta}$ was promoted. Regarding the secretion pattern of TNF-${\alpha}$ according to the treatment of PMA, its secretion amount was incredibly increased by concurrent treatment of WP, however, in case of co-treatment of WP with PMA and DNCB, it was found that the secretion amount of TNF-${\alpha}$ decreased. Conclusions : In this study, the WP extracting substance was confirmed that it had an influence on expression patterns of cytokine genes according to the actions of a variety kinds of immune reaction inductive substances treated on the THP-1 cells. Especially, WP co-treatment with PMA and DNCB was suppressed the expression of inflammatory cytokines, such as IL-$1{\alpha}$, IFN-${\gamma}$ and TNF-${\alpha}$.