• Natural Product Sciences
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• v.13 no.3
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• pp.207-213
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• 2007

Scutellaria baicalensis is known as a herbal medicine with anti-inflammatory and anti-oxidative activities. However, effect of Scutellaria baicalensis on lupus pathogenesis that is characterized by overproduction of proinflammatory cytokines and abnormalities in regulation, function, and interaction of immune cells remains unclear. We investigated effects of Scutellariae radix methanol extract (SBMeOH) on the production of proinflammatory cytokines and abnormal activation of T cells in vitro in pristane-induced lupus BALB/c mice. These results demonstrated that SBMeOH significantly decreased the LPS-stimulated production of $TNF-{\alpha}$, IL-6, and IL-10 by splenic and peritoneal macrophages and IL-6 and IL-10 by splenocytes from pristane-induced lupus mice. SBMeOH significantly downregulated the Con A-stimulated overproduction of IL-6, IL-10, and $IFN-{\gamma}$ by splenocytes from pristane-induced lupus mice. Also, SBMeOH significantly attenuated the Con A-induced expression of CD4+ T cells and CD69+CD4+ T cells but not CD8+ T cells in pristane-induced lupus mice. Our findings indicate that SBMeOH may ameliorate lupus pathogenic inflammation and autoimmunity via downregulation of proinflammatory cytokine production and abnormal activation of T cells.

• IMMUNE NETWORK
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• v.7 no.1
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• pp.10-17
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• 2007

Autoimmune arthritis, such as rheumatoid arthritis (RA), is a chronic inflammatory disorder that primarily affects the joints and then results in their progressive destruction. Effector Th cells have been classified as Th1 and Th2 subsets based on their cytokine expression profiles and immune regulatory function. Another subset of T cells termed Th17 was recendy discovered and known to selectively produce IL-17. Also, Th17 was shown to be generated by TGF${\beta}$ and IL-6 and maintained by IL-23. IL-17 is a proinflammatory cytokine that is considered to involve the development of various inflammatory autoimmune diseases such as RA, asthma, lupus, and allograft rejection. IL-17 is present in the sera, synovial fluids and synovial biopsies of most RA patient. IL-17 activates RA synovial fibroblasts to synthesize IL-6, IL-8 and VEGF via PI3K/Akt and NF-${\kappa}B$ dependent pathway. IL-17 increases IL-6 production, collagen destruction and collagen synthesis. In addition, it not only causes bone resorption but also increases osteoclastogenesis and fetal cartilage destruction. Inhibition of the IL-17 production may contribute a novel therapeutic approach along with potent anti-inflammatory effect and with less immunosuppressive effect on host defenses.

• The Korean Journal of Food And Nutrition
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• v.19 no.2
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• pp.201-206
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• 2006

Numerous investigators have studied various activities of natural products and have found that they have not only nutritional effects, but also beneficial properties to cure various diseases and to maintain good health. Job's Tear(Yul-Moo) is a grass crop that has long been used in traditional medicine and as a nourishing food. Although its mechanism of action remains unclear, Job's Tear has been reported to exhibit anti-inflammatory, stomachic, anti-allergic, and anti-spastic effects and has been used in China for the treatment of warts, rheumatism, and neuralgia. Previous results in our laboratory demonstrated that the ethanol extract and the water extract of Job's Tear exerted an immune regulatory function on mice cells in vitro. The present study was performed to investigate the ex vivo effect of Job's Tear on immune function. Seven to eight weeks old mice(Balb/c) were fed chow diet ad libitum and water extract of Job's Tear was administered orally every other day for four weeks at two different concentrations(50 and 500mg/kg B.W.). Splenocytes proliferation with mitogen stimulation with Con A and LPS was enhanced at 50 mg/kg B.W. of Job's Tear compared to those of the control group. The results of this ex vivo study showed that proliferation of splenocytes and macrophage activation were seen in the mice orally administrated 50 mg/kg B.W. of Job's Tear water extracts. In conclusion, this study suggests that Job's Tear extracts may enhance immune function by regulating splenocyte proliferation and the cytokine prodution capacity of activated macrophages in mice.

• Journal of Microbiology and Biotechnology
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• v.32 no.9
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• pp.1186-1194
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• 2022

The intake of probiotic lactic acid bacteria not only promotes digestion through the microbiome regulated host intestinal metabolism but also improves diseases such as irritable bowel syndrome and inflammatory bowel disease, and suppresses pathogenic harmful bacteria. This investigation aimed to evaluate the immunomodulatory effects in intestinal epithelial cells and to study the clinical efficacy of the selected the Bifidobacterium breve and Bifidobacterium longum groups. The physiological and biochemical properties were characterized, and immunomodulatory activity was measured against pathogenic bacteria. In order to find out the mechanism of inflammatory action of the eight viable and sonicated Bifidobacterium spp., we tried to confirm the changes in the pro-inflammatory cytokines (TNF-α, interleukin (IL)-6, IL-12) and anti-inflammatory cytokine (IL-10), and chemokines, (monocyte chemoattractant protein-1, IL-8) and inflammatory enzymatic mediator (nitric oxide) against Enterococcus faecalis ATCC 29212 infection in Caco-2 cells and RAW 264.7 cells. The clinical efficacy of the selected B. breve and B. longum group was studied as a probiotic adjuvant for acute diarrhea in children by oral administration. The results showed significant immunomodulatory effects on the expression levels of TNF-α, IL-6, IL-12, MCP-1, IL-8 and NO, in sonicated Bifidobacterium extracts and viable bifidobacteria. Moreover, each of the Bifidobacterium strains was found to react more specifically to different cytokines. However, treatment with sonicated Bifidobacterium extracts showed a more significant effect compared to treatment with the viable bacteria. We suggest that probiotics functions should be subdivided according to individual characteristics, and that personalized probiotics should be designed to address individual applications.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.235-241
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• 2004

Gagam-danguiemja (GDGJ), a traditional Korean prescription, has been used as therapeutics for atopic allergic diseases such as atopic dermatitis. To evaluate the atopic allergic effect of modified GDGJ, we investigated a possible effect of GDGJ on mast cell-mediated allergic reaction, cytokinases secretion and mRNA expression in vivo and in vitro. Mast cells are a potent source of mediators that regulate the inflammatory response in allergic reaction. In mice orally administered by GDGJ (0.01, 0.1 and 1.0 g/kg) for 1 h, compound 48/80-induced ear oedema was significantly reduced. TNF-${\alpha}$, IL-8, and IL-6 secretion were inhibited by GDGJ in the human mast cell line (HNC-1). But TNF-${\alpha}$, IL-8, and IL-6 mRNA expression were not inhibited by GDGJ at the dose of 0.01 mg/ml. These findings may help in understanding the mechanism of action of this herbal medication, leading to the control of mast cells in atopic allergic reaction like AD.

• Biomedical Science Letters
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• v.20 no.4
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• pp.244-249
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• 2014

Arazyme is a metalloprotease secreted by Aranicola proteolyticus that was previously shown to suppress cytokine expression of keratinocytes and endothelial cells and inhibit histopathological features in an atopic dermatitis-like animal model. However, the regulatory effects of arazyme in other allergic diseases have yet to be elucidated. In this study, we investigated whether arazyme is effective against neutrophil apoptosis in allergic diseases such as allergic rhinitis and asthma. Arazyme inhibited neutrophil apoptosis of normal subjects in a dose-dependent manner. However, the antiapoptotic effect of arazyme was reversed by LY294002, an inhibitor of PI3K, AKTi, an inhibitor of Akt, PD98059, an inhibitor of MEK, and BAY-11-7085, an inhibitor of NF-${\kappa}B$. Arazyme induced activation of NF-${\kappa}B$ via PI3K/Akt/ERK pathway. The anti-apoptotic effect of arazyme is associated with inhibition of cleavage of caspase 3 and caspase 9. Arazyme inhibited constitutive apoptosis of neutrophil in a dose-dependent manner in allergic subjects, and its mechanism was shown to be associated with PI3K/Akt/ERK/NF-${\kappa}B$. The results presented here improve our understanding of neutrophil apoptosis regulation and will facilitate development of drugs for treatment of allergic diseases.

• YAKHAK HOEJI
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• v.55 no.6
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• pp.456-461
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• 2011

The aim of the present study is to investigate the anti-inflammatory effect of a Rice Bran Ethanol Extract (RBE). Inflammation, such as a bacterial infection in vivo metabolites, such as external stimuli or internal stimuli to the defense mechanisms of the biological tissue a variety of intracellular regulatory factors deulin inflammatory TNF-${\alpha}$, IL-$1{\beta}$, IL-6, IL-8, such as proinflammatory cytokines, prostagrandin, lysosomal enzyme, free radicals are involved in a variety of mediators. The present study was designed to determine the effect of the RBE on pro-inflammatory factors such as NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 in lipopolysaccharide (LPS) - stimulated RAW264.7 macrophages cells. The cell toxicity was determined by MTS assay. To evaluate of anti-inflammatory effect of RBE, amount of NO was measured using the NO detection kit and the iNOS expression was measured by reverse transcriptase polymerase chain reaction (RT-PCR). And proinflammatory cytokines were measured by ELISA kit. As a result, the RBE reduced NO, iNOS expression and TNF-${\alpha}$, IL-$1{\beta}$, IL-6 production without cytotoxicity. Our results suggest that the RBE may have an anti-inflammatory property through suppressing inflammatory mediator productions and appears to be useful as an anti-inflammatory material.

• Journal of Periodontal and Implant Science
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• v.27 no.4
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• pp.883-908
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• 1997

Bone remodeling is characterized by the coupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. The process is tightly regualted at the local level by an incompletely known netwotk of peptide and non-peptide fators. Nitric oxide(NO), synthesized by nitric oxide synthetase(NOS) from L-arginine, is becoming recognized as an important bioregualtory molecule in a variety of tissue, but little is known about its possible role in periodontal tissue. The purpose of this study is to investigate the expression of nitric oxide synthetase(NOS) in inflamed gingiva and the effects of cytokine on the expression of NOS protein. The expression of NOS in gingival tissue was evaluated by immunohistochemical staining for $NOS_1$, $NOS_2$, $NOS_3$. The effect of cytokine on the expression of NOS in human periodontal ligament cells and osteoblast-like HOS cells by western blot analysis. Further, we studied that NO functions in periodontal ligament cells as a regulatory molecule. PDL cells incubated with NOS inhibitor and donor. The protein expression, type I collagen & non-collagenous protein, nitrate production and cell proliferation were evaluated The results were as follows. 1. $NOS_1$, $NOS_2$, $NOS_3$ was rarely distributed in healthy gingiva, but stronger stained in gingival epithelium, endothelial cells, and mononuclear cells of inflammed gingiva. 2. The cytokine stimulated $NOS_1$, and $NOS_3$ protein were not inducing or inhibitory effect to compared with control in PDL and HOS cells. 3.Incubation of cells with combination of $TNF-{\alpha}$, $IFN-{\gamma}$, LPS result in a time dependant increase in $NOS_2$ expression, reaching a maximal level after 24 hours of stimulation. 4. The osteonectin protein inhibitory effect of NMA, inhibitor of NOS, was reversed by Larginine in dose dependant manner. 5. NMA decreased cell poliferation and nitrate production, but the inhibitory efffect of NMA was also prevented by the NO donor, sodium nitropruiside. These results suggest that exogenously synthesized NO was playing a stimulating effect on cell proliferation or on non-collagenous protein expression. Therefore NO have an important role in mediation of localized bone destruction associated inflammatory bone disease such as periodontitis.

• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.454-460
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• 1993

Abnormalities of the T cell subsets have been detected in the immunologically mediated disease sites such as periodontal lesions which are attributable to the regulatory effect of cell differentiation and specific chemokinetic effect of various cytokines. Macrophage Inflammatory protein$(MIP)-1{\alpha}$ and gammain terferon$({\gamma}-IFN)$ serve as important immunoregulatory molecules through which growth and differentiation of specific T cell subsets are known to be negatively regulated. Murine cytolytic T cell line CTLL-2 were used to perform the [$^3H$]-thymidine incorporation test, by which we obtained more comprehensive view in regulatory actions of cytokines on the T cell subset proliferation. 1. $rMIP-{\alpha}$(200ng/ml) and $r{\gamma}-IFN$(100U/ml) appreared to suppress the proliferation rate to CTLL-2 by 74 and 86% respectively, and the suppressive action of two cytokines were synergisic. 2. Culture supernatant of anti-CD3 mAb-stimulated mouse splenocyte enhanced the proliferation rate of CTLL-2 up to 10-fold with dose-dependent manner. However, culture supernatant of unstimulated splenocyte showed only 2-fold increase in the proliferation rate. 3. CTLL-2 cell proliferation was strictly IL-2 dependent.

• Journal of Microbiology and Biotechnology
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• v.27 no.12
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• pp.2237-2240
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• 2017

In the present study, we investigated the effect of tyndallized HY7712 (tHY7712) on the expression of Th cell specific transcription factors and cytokines in whole-body ${\gamma}$-irradiated mice. Oral administration of tHY7712 strongly recovered the ${\gamma}$-irradiation-suppressed expression of helper T (Th) cell- and regulatory T cell-related transcription factors and cytokines, such as T-bet, Foxp3, IFN-${\gamma}$, TNF-${\alpha}$, and IL-10, and suppressed Th2 cell-associated transcription factor and cytokine GATA3 and IL-5, respectively. Furthermore, compared with the control, tHY7712 treatment also restored ${\gamma}$-irradiation-impaired natural killer and cytotoxic T cell activities against YAC-1 tumor cells to 97.8% and 98.6%, respectively.