• Parasites, Hosts and Diseases
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• v.46 no.3
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• pp.145-151
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• 2008

During Toxoplasma gondii infection, macrophages, dendritic cells, and neutrophils are important sources of pro-inflammatory cytokines from the host. To counteract the pro-inflammatory activities, T. gondii is known to have several mechanisms inducing down-regulation of the host immunity. In the present study, we analyzed the production of pro- and anti-inflammatory cytokines from a human myelomonocytic cell line, THP-1 cells, in response to treatment with T. gondii lysate or lipopolysaccharide (LPS). Treatment of THP-1 cells with LPS induced production of IL-12, TNF-$\alpha$, IL-8, and IL-10. Co-treatment of THP-1 cells with T. gondii lysate inhibited the LPS-induced IL-12, IL-8 and TNF-$\alpha$ expression, but increased the level of IL-10 synergistically. IL-12 and IL-10 production was down-regulated by anti-human toll-like receptor (TLR)-2 and TLR4 antibodies. T. gondii lysate triggered nuclear factor (NF)-${\kappa}B$-dependent IL-8 expression in HEK293 cells transfected with TLR2. It is suggested that immunosuppression induced by T. gondii lysate treatment might occur via TLR2-mediated NF-${\kappa}B$ activation.

• Molecules and Cells
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• v.38 no.1
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• pp.26-32
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• 2015

Toll-like receptors (TLR) 7 and 9 transduce a cellular signal through the MyD88-dependent pathway and induce the production of inflammatory mediators against microbial nucleotide components. The repeated stimulation of TLR4 leads to endotoxin tolerance, but the molecular mechanisms of tolerance induced through the costimulation of individual TLR has not yet been established, although endosomal TLRs share signaling pathways with TLR4. In the present study, mouse macrophages were simultaneously stimulated with the TLR7 agonist, gardiquimod (GDQ), and the TLR9 agonist, CpG ODN 1826, to examine the mechanism and effector functions of macrophage tolerance. Compared with individual stimulation, the costimulation of both TLRs reduced the secretion of TNF-${\alpha}$ and IL-6 through the delayed activation of the NF-${\kappa}B$ pathway; notably, IL-10 remained unchanged in costimulated macrophages. This tolerance reflected the early induction of suppressor of cytokine signaling-1 (SOCS-1), according to the detection of elevated TNF-${\alpha}$ secretion and restored NF-${\kappa}B$ signaling in response to the siRNA-mediated abrogation of SOCS-1 signaling. In addition, the restimulation of each TLRs using the same ligand significantly reduced the expression of both TLRs in endosomes. These findings revealed that the costimulation of TLR7 and TLR9 induced macrophage tolerance via SOCS-1, and the restimulation of each receptor or both TLR7 and TLR9 downregulated TLR expression through a negative feedback mechanisms that protects the host from excessive inflammatory responses. Moreover, the insufficient and impaired immune response in chronic viral infection might also reflect the repeated and simultaneous stimulation of those endosomal TLRs.

• Journal of Microbiology and Biotechnology
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• v.23 no.3
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• pp.414-421
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• 2013

Lactic acid bacteria (LAB) in fermented foods have attracted considerable attention recently as treatment options for immune diseases, the incidence of which has been increasing worldwide. The ability of 500 strains of LAB, isolated from kimchi, to induce TNF-${\alpha}$ production in peritoneal macrophages was investigated. Lactobacillus plantarum HY7712 most strongly induced TNF-${\alpha}$ production as well as NF-${\kappa}B$ activation. However, HY7712 inhibited NF-${\kappa}B$ activation in LPS-stimulated peritoneal macrophages. When HY7712 was orally treated in cyclophosphamide (CP)-immunosuppressed mice for 5 or 15 days, it reversed the body and spleen weights, blood RBC and WBC levels, and splenocyte and bone marrow cells that were reduced by CP. Orally administered HY7712 increased concanavalin A-induced T cell proliferation to 84.5% of the normal group on day 15, although treatment with CP alone markedly reduced it to 53.7% of the normal group. Furthermore, orally administered HY7712 significantly induced the expressions of IL-2 and IFN-${\gamma}$ in ConA-induced splenic cytotoxic T cells of CP-treated mice. Orally administered HY7712 restored the CP-impaired phagocytosis of macrophages in mice. Orally administered HY7712 also restored the cytotoxicity of NK and cytotoxic T cells derived from spleen and bone marrow against YAC-1 in CP-immunosuppressed mice. Based on these findings, orally administered HY7712 may accelerate the recovery of cyclophosphamide-caused immunosuppression, without evident side effects, by immunopotentiating NK and Tc cells, and may provide a mechanistic basis for using HY7712 as an alternative means in lessening chemotherapyinduced immunosuppression in cancer patients.

• Natural Product Sciences
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• v.27 no.2
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• pp.115-121
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• 2021

Lentinus edodes contains functional metabolites such as polysaccharopeptides, lectins, and secondary metabolites. Fermented soybean paste is representative fermented materials in Korea, and is gradually increasing due to various biological activities. In the present study, ethanol extracts of fermented products with/without L. edodes were designated as SPL and SP, and prepared to develop safer and therapeutic functional foods with antioxidant and anti-inflammatory activities for treatment of inflammatory disorders. SP and SPL extracts exhibited antioxidant effects via inhibiting radical activities. Inflammatory mediators, nitric oxide (NO), prostaglandin E₂ (PGE₂), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase (iNOS) production and nuclear factor-kappa B (NF-κB) activation were down-regulated by two extracts. SPL extract more strongly enhanced the antioxidant and anti-inflammatory activities than SP extract. Its' activities shown more longer fermentation period and more strong inhibitory effects. Taken together, our results suggested that fermented product with medicinal plant has synergic effect and SPL can be a potential candidate for treatment of inflammatory bowel diseases.

• Herbal Formula Science
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• v.26 no.1
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• pp.1-12
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• 2018

Objectives : Cheongnoimyungshin-hwan (CNMSH) is a Herbal compound prescription that is composed mainly of herbal medicines such as Ginseng Radix Alba, Angelicae Gigantis Radix, Dioscoreae Rhizoma, Longan Arillus and cornus cervi parvum, and for the purpose of improving memory and preventing dementia. Methods : In this study, it was investigated whether CNMSH could suppress inflammatory response and oxidative stress in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. As a result, CNMSH decreased expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, and also inhibited production of NO, prostaglandin E2. Results : This effect was associated with the suppression of the expression of p65, one of the nuclear factor-kappaB ($NF-{\kappa}B$) subunits, and increased expression of $I{\kappa}B-{\alpha}$, inhibit the $NF-{\kappa}B$ transcription factor. In addition, CNMSH significantly blocked intracellular reactive oxygen species accumulation in response to LPS stimulation. Furthermore, CNMSH increased expression of nuclear factor erythroid 2-related factor (Nrf)-2 activation and heme oxygenase (HO)-1. Conclusions : Therefore, it has been shown anti-inflammatory and antioxidant effects by inhibiting the expression and production of inflammatory mediators in LPS-stimulated macrophages, and is associated with ROS generation and is activated by Nrf2/HO-1 signaling pathway.

• Herbal Formula Science
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• v.22 no.1
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• pp.79-92
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• 2014

Objectives : The aim of this study was identification of the anti-oxidative and anti-inflammatory effects of Talmyung-san (TMS) in mouse macrophage, RAW264.7 cells. Methods : To identify the anti-oxidative effect of TMS, scavenging activities of DPPH radical, nitric oxide and peroxynitrite were measured in vitro. In RAW264.7 cells, DCFH-DA assay was conducted to examine the inhibitory effect of TMS on ROS production in response to lipopolysaccharide. And the productions of nitric oxide (NO), $PGE_2$ and pro-inflammatory cytokines were measured. The levels of COX-2, iNOS, nuclear NF-${\kappa}B$ p65 expression and phosphorylation of $I{\kappa}B-{\alpha}$ in cytosol were detected by western blotting analyses. Results : TMS couldn't scavenged DPPH radical, but nitric oxide and peroxynitrite were decreased. TMS decreased intracellular ROS, NO, and IL-$1{\beta}$ production effectively. However, TMS inhibited $PGE_2$ levels only in high concentration ($300{\mu}g/m{\ell}$) and TMS failed to suppress the production of IL-6 and TNF-${\alpha}$. Results from immunoblot analyses revealed that TMS decreased activation of COX-2, iNOS, phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Conclusions : TMS has anti-RNS and anti-inflammatory effects via NF-${\kappa}B$ pathway and more intensive studies will be required to evaluate therapeutic potential of TMS.

• The Korea Journal of Herbology
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• v.28 no.2
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• pp.67-73
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• 2013

Objective : Lithospermum Erythrorhizon (LE) has been used as an anti-bacterial and anti-inflammatory agent. However, it is unclear that LE aqueous extract could show the anti-inflammatory effects in RAW 264.7cells. The purpose of this study was to investigate the anti-inflammatory effect of aqueous extract from LE on lipopolysaccharide (LPS) - induced inflammatory response. Methods : To measure out the cytotoxicity of LE, we performed the MTT assay. To evaluate the anti-inflammatory effects of LE, we examined the inflammatory mediators such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, interleukin, (IL)-$1{\beta}$ and (IL)-6) on RAW 264.7 cells. We also examined molecular mechanisms such as mitogen-activated protein kinases (MAPKs) and nuclear factor-B (NF-${\kappa}B$) activation by western blot. Results : Aqueous Extract from LE itself did not have any cytotoxic effect in RAW 264.7 cells. Aqueous extract from LE inhibited LPS-induced productions of inflammatory mediators such as NO, $PGE_2$, and pro-inflammatory cytokines including TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 in RAW 264.7cells. In addition, LE inhibited the phosphorylation of p38 kinases (p38), c-Jun $NH_2$-terminal kinase (JNK), and NF-${\kappa}B$ activation in RAW 264.7 cells. Conclusion : LE down-regulated LPS-induced production of inflammatory mediators through the inhibition of p38, JNK and NF-${\kappa}B$ activation. Taken together, these results could provide the evidence for the anti-inflammatory effects of LE. Therefore, LE may be a novel target in the management of inflammation and help to support a potential strategy for prevention and therapy of inflammatory diseases.

• The Journal of Korean Medicine
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• v.29 no.1
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• pp.179-191
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• 2008

Background and Objectives : Atopic dermatitis is a recurrent or chronic eczematous skin disease with severe pruritus,and has increased in Korea. Although the pathogenic mechanisms of atopic dermatitis are yet unknown, recently skin barrier dysfunction and hyperresponsive Th2 cells in the acute phase have been reported as important mechanisms. Cheonggi-san(CGS) is used in oriental clinics for treatingacute skin lesions of eczema or urticaria. There have been no studies on the therapeutic mechanism of CGS for curing atopic dermatitis. We aimed to find out the therapeutic effects of its internaluse on atopic dermatitis-like skin lesions, induced in NC/Nga mice by the mite antigen D. pteronyssinus and disrupting skin barrier. Materials and Methods : The NC/Nga mice were classified into three groups: control group, atopic dermatitis elicitated group(AD), and CGS treated group (CT). Atopic dermatitis-like skin lesions were induced on the back of female NC/Nga mice, 12 weeks of age, by tape stripping, 5% SDS applied to disrupt skin barrier and painting 3 times a week with D. pteronyssinus crude extract solution for 3 weeks. CT was treated with CGS orally after atopic dermatitis was elicitated. We observed changes of skin damage, mast cells, substance P, angiogenesis, skin barrier, Th2 cell differentiation, nuclear factor-${\kappa}B(NF-{\kappa}B)$ p65 activation and COX-2 in NC/Nga mice with atopic dermatitis-like skin lesions. Results : The skin damages as eczema were seenin AD, but mitigated in CT. The degranulated mast cells in dermal papillae increased in AD, but decreased in CT. The substance P positive reacted cells in CT remarkably decreased. The angiogenesis increased in AD, but decreased in CT. The decrease of lipid deposition and ceramide in AD was seen, but anincrease of lipid deposition and ceramide in CT was seen. The distribution of IL-4 positive reacted cells in dermal papillae increased in AD, but decreased in CT. The distribution of NF-${\kappa}B$ p65 positive reacted cells & COX-2 positive reacted cells in CT decreased. Conclusion : The results may suggest that the CGS per os decreases the dysfunction of the skin barrier, inhibits Th2 cell differentiation and inhibits NF-${\kappa}B$ p65 activation in NC/Nga mice with atopic dermatitis-like skin lesions.

• Molecules and Cells
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• v.45 no.10
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• pp.749-760
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• 2022

Osteoclast generation from monocyte/macrophage lineage precursor cells needs to be tightly regulated to maintain bone homeostasis and is frequently over-activated in inflammatory conditions. PARK2, a protein associated with Parkinson's disease, plays an important role in mitophagy via its ubiquitin ligase function. In this study, we investigated whether PARK2 is involved in osteoclastogenesis. PARK2 expression was found to be increased during the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. PARK2 gene silencing with siRNA significantly reduced osteoclastogenesis induced by RANKL, LPS (lipopolysaccharide), TNFα (tumor necrosis factor α), and IL-1β (interleukin-1β). On the other hand, overexpression of PARK2 promoted osteoclastogenesis. This regulation of osteoclastogenesis by PARK2 was mediated by IKK (inhibitory κB kinase) and NF-κB activation while MAPK (mitogen-activated protein kinases) activation was not involved. Additionally, administration of PARK2 siRNA significantly reduced osteoclastogenesis and bone loss in an in vivo model of inflammatory bone erosion. Taken together, this study establishes a novel role for PARK2 as a positive regulator in osteoclast differentiation and inflammatory bone destruction.

• Korean Journal of Plant Resources
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• v.34 no.3
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• pp.216-222
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• 2021

Ulcerative colitis (UC) is an inflammatory bowel disease and a chronic gastrointestinal disorder. Rubi Fructus (RF), the fruit of Rubus coreanus Miquel, is known to exert several pharmacological effects including anti-oxidative, anti-obesity and anti-inflammatory properties. However, the improving effect and mechanism of RF on intestinal inflammation is not been fully understood. The purpose of this study was to investigate the regulatory effect of RF on dextran sulfate sodium (DSS)-induced colitis in mice. We evaluated the effects of RF on DSS-induced clinical signs by analyzing weight loss and colon length. The inhibitory effects of RF on inflammatory mediators such as prostaglandin E₂ (PGE₂), cyclooxygenase (COX)-2, as well as the activation of nuclear factor-κB (NF-κB), were determined in colitis tissue. Our data indicated that mice treated with DSS showed clinical symptoms of colitis, including weight loss, colon length decrease and diarrhea. However, we observed that RF treatment significantly improved these clinical symptoms of weight loss, colon length decrease and diarrhea induced by DSS. RF inhibited the enhanced levels of COX-2 and PGE₂ caused by DSS. We also showed that the anti-inflammatory mechanism of RF by suppressing the activation of NF-kB in DSS-treated colon tissues. Collectively, the findings of this study indicate the prospect of developing new drugs from RF for UC treatment.