• Biomolecules & Therapeutics
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• v.26 no.4
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• pp.417-423
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• 2018

Extracellular interleukin 1 alpha (IL-$1{\alpha}$) released from keratinocytes is one of the endpoints for in vitro assessments of skin irritancy. Although cells dying via primary skin irritation undergo apoptosis as well as necrosis, IL-$1{\alpha}$ is not released in apoptotic cells. On the other hand, active secretion has been identified in interleukin-1 receptor antagonist (IL-1ra), which was discovered to be a common, upregulated, differentially-expressed gene in a microarray analysis performed with keratinocytes treated using cytotoxic doses of chemicals. This study examined whether and how IL-1ra, particularly extracellularly released IL-1ra, was involved in chemically-induced keratinocyte cytotoxicity and skin irritation. Primary cultured normal adult skin keratinocytes were treated with cytotoxic doses of chemicals (hydroquinone, retinoic acid, sodium lauryl sulfate, or urshiol) with or without recombinant IL-1ra treatment. Mouse skin was administered irritant concentrations of hydroquinone or retinoic acid. IL-1ra (mRNA and/or intracellular/extracellularly released protein) levels increased in the chemically treated cultured keratinocytes with IL-$1{\alpha}$ and IL-$1{\beta}$ mRNAs and in the chemically exposed epidermis of the mouse skin. Recombinant IL-1ra treatment significantly reduced the chemically-induced apoptotic death and intracellular/extracellularly released IL-$1{\alpha}$ and IL-$1{\beta}$ in keratinocytes. Collectively, extracellular IL-1ra released from keratinocytes could be a compensatory mechanism to reduce the chemically-induced keratinocyte apoptosis by antagonism to IL-$1{\alpha}$ and IL-$1{\beta}$, suggesting potential applications to predict skin irritation.

• Applied Biological Chemistry
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• v.48 no.4
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• pp.315-321
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• 2005

The effects of the extracts from the bran part of pigmented rices on inflammation was evaluated by determining their inhibitory action on the histamine and ${\beta}-hexosaminidase$ release, together with inflammatory cytokine productions ($IL-1{\beta},\;TNF-{\alpha}$ and IL-6). Examination of the inhibitory effects on the histamine and ${\beta}-hexosaminidase$ release from a basophilic cell line RBL-2H3 cells and rat peritoneal mast cells (RPMC) showed that the pigmented rice extract inhibited these inflammation-mediating substances (10.19% and 110.03% inhibition in histamine and ${\beta}-hexosaminidase$ release, respectively), while normal brown rice extract rather increased their release. For RPMC, the pigmented rice extract was found to have 8 or 3-fold stronger inhibitory activity than normal brown rice toward histamine or ${\beta}-hexosaminidase$ release, respectively. Expression of $IL-1{\beta},\;TNF-{\alpha}$ and IL-6 was measured as the representative inflammatory cytokine species showed that the pigmented rice extract had a higher inhibitory activity than the normal rice counterpart. ELISA analysis for determining cytokine release demonstrated a more effective blockading ability of the pigmented rice to the release of $IL-{\beta},\;TNF-{\alpha}$ and IL-6 compared to normal rice. These results showed us the superiority of the pigmented rice bran extract not only in suppressing the release of inflammation-mediating substances such as histamine and ${\beta}-hexosaminidase$, but also in repression of the inflammatory cytokine expression.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.1
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• pp.23-35
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• 2009

Objectives The purpose of this study is to investigate the effect of Kakamsodokum (KKSDU) on atopic dermatitis in an in-vitro experiment using an NC/Nga atopic dermatitis mouse, which has histological and clinical similarities to the condition in humans. Methods We evaluated $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $TGF-{\beta}$, IL-10 mRNA, CD4+/$IFN-{\gamma}+$, and CD4+CD25+foxp3+ in B and T cells of NC/Nga atopic dermatitis mouse by real-time PCR and intracellular staining in vitro. Results KKSDU medicines supressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, $TGF-{\beta}$ mRNA and increased IL-10 mRNA in B cells. CD4+/$IFN-{\gamma}+$ and CD4+CD25+foxp3+ in T cells were increased by KKSDU. Conclusions KKSDU on atopic dermatitis might be very effective to the atopic dermatitis treatment.

• Journal of Pharmacopuncture
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• v.4 no.1
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• pp.5-21
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• 2001

The influence of electroacupuncture (EA), a traditional Chinese medical treatment, on type Ⅱ collagen-induced arthritis (CIA) was examined in DBA/1J mice in vivo. Mice were immunized intradermally twice at the 3-week interval with bovine type Ⅱ collagen(C Ⅱ). EA stimulation, begun on the 21 simultaneously with the second immunization, was applied at the acupoint equivalent to GV4 three times a week for 3 weeks. The results showed that EA delayed the onset, attenuated the severity of arthritis, and reduced the anti-collagen antibody level. Furthermore, we investigated the impact of EA on the productions of endogenous $interleukin-1{\Beta}$ (IL-1 beta) and prostaglandin E2 (PGE2), and the levels of IL-1 beta mRNA in splenocytes and synovial tissues from C Ⅱ immunized mice on the 45 and cyclooxygenase-2 (COX-2) mRNA in lipopolysaccharide (LPS)-stimulated macrophages of normal mice by using reverse transcriptase-polymerase chain reaction (RT-PCR). EA stimulation significant inhibited the concentrations of splenic endogenous IL-1 beta and serum PGE2. The expression of IL-1 beta mRNA in spleen cells was obviously down-regulated and that in synovial tissues was modestly affected by EA. COX-2 mRNA was highly expressed in cultured peritoneal macrophages when stimulated with LPS. Previous treatment with EA also reduced LPS-stimulated induction of COX-2 mRNA. These data suggest that EA has an inhibitory effect on murine CIA, and the partial mechanism of its therapeutic result may be attributed to inhibiting the productions of IL-1 beta and PGE2 by suppression the IL-1 beta and COX-2 gene activations.

• Journal of the Korean Society of Physical Medicine
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• v.9 no.2
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• pp.193-200
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• 2014

PURPOSE: This study examined the effects of treadmill exercise of diverse intensities on the expression of IL-$1{\beta}$ (interleukine-$1{\beta}$) in the spinal cord in osteoarthritis rats. METHODS: The authors applied treadmill exercise of diverse intensity for 4 weeks to Sprague-Dawley rats to which intra-articular injection of monosodium iodoacetate(MIA, $3mg/50{\mu}l$, diluted in saline) was applied in the right knee joint to induce osteoarthritis. The four-week exercise was not applied to the control group(CG, n=15), while exercise of applicable intensity was applied to the low-intensity exercise group(LEG, n=15), moderate-intensity exercise group (MEG, n=15), and high-intensity exercise group(HEG, n=15) for four weeks. Observations were made of expression of IL-$1{\beta}$ in the spinal cord in osteoarthritis rats using western blot analysis. RESULTS: There were significant differences(p<.05) in the comparison of expression of IL-$1{\beta}$ in the spinal cord between the four groups involved. And the LEG and MEG had reduced expression of IL-$1{\beta}$ significantly than the CG(p<.05); in particular, the MEG showed the lowest expression. On the other hand, the HEG had more elevated expression of IL-$1{\beta}$ significantly than the CG(p<.05). CONCLUSION: As a result, factors that induce neuropathic pain such as IL-$1{\beta}$ are reduced; thus, the recovery of damaged neurons is improved and neuropathic pain is reduced. Further, when prescribing exercise to treat osteoarthritis patients, exercise of moderate intensity suitable for patients' physical conditions, rather than high intensity, maximizes the effects of this therapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.4
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• pp.1044-1050
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• 2006

The Korean genuine medicine, 'Gigukjihwangtanggami (GJT)' has long been used clinically for hypertension and various cerebrovascular diseases. However, experimental study has been carried out very little. Recently cytokines involved in the regulation of inflammatory reactions and immune responses may play an important role in the pathogenesis of cerebral infarction (CI). The aim of this study is to investigate the effect of GJT on the production of pro-inflammatory cytokines and anti-inflammatory cytokines in peripheral blood mononuclear cells (PBMCS) stimulated with lipopolysaccaride (LPS) from Cl patients. The amount of tumor necrosis $factor-{\alpha}\;(TNF-{\alpha}),\;interleukin-1{\beta}\;(IL-1{\beta})$, IL-6, IL-8, IL-4 and IL-10 in PBMC culture supernatant was significantly increased in the LPS treated cells compared to unstimulated cells. GJT inhibited the production of $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 induced by LPS. The maximal inhibition rate of the $TNF-{\alpha},\;IL-1{\beta}$, IL-6 and IL-8 production by pretreatment of GJT (1 mg/ml) was $57.32{\pm}2.5%$ (p.0.05), $42.02{\pm}3.5%$ (p.0.05), $40.02{\pm}2.3%$ (p.0.05) and $48.02{\pm}3.1$, (p.0.05), respectively. In the Other hand, GJT increased the production of IL-4 and IL-10. The maximal increase rate of the IL-4 and IL-10 production by pretreatment of GJT (1 mg/ml) was $42.4{\pm}3.3%$ (p.0.05) End $56.4{\pm}2.9%$ (p.0.05), respectively. Taken together, these results indicate that GJT Ray have regulatory effects on the cytokine production and suggest that GJT might use clinically for the treatment of CI.

• Archives of Pharmacal Research
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• v.26 no.12
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• pp.1029-1035
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• 2003

Osteoporosis is recognized as one of the major hormonal deficiency diseases, especially in menopausal women and the elderly. When estrogen is reduced in the body, local factors such as IL-1 $\beta$ and IL-6, which are known to be related with bone resorption, are increased and promote osteoclastogenesis, which is responsible for bone resorption. In the present study, we investigated whether glucosidic isoflavones (Isocal, PIII) extracted from Sophorae fructus affect the proliferation of osteoblasts and prevent osteoclastogenesis in vitro by attenuating upstream cytokines such as IL-1$\beta$ and IL-6 in a human osteoblastic cell line (MG-63) and in a primary osteoblastic culture from SD rat femurs. Interestingly, IL-1$\beta$ and IL-6 mRNA were significantly suppressed in osteoblast-like cells treated with 17$\beta$-estradiol (E2) and PIII when compared to positive control (SDB), and this suppression was more effective at $10^{-8}$% than at the highest concentration of $10^{-4}$%. In addition, these were confirmed in protein levels using ELISA assay. In the cell line, the cells showed that E2 was the most effective in osteoblastic proliferation over the whole range of concentration ($10^{-4}%-10^{-12}$%), even though PIII also showed the second greatest effectiveness at $10^{-8}$%. Nitric oxide (NO) was significantly (p<0.05) upregulated in PIII and E2 over the concentration range $10^{-6}% to 10^{-8}$% when compared to SDB, without showing any dose dependency. In bone marrow primary culture, we found by TRAP assay that PIII effectively suppressed osteoclastogenesis next to E2 in comparison with SDB and culture media (control). In conclusion, these results suggest that local bone-resorbing cytokines can be regulated by PIII at lower concentrations and that, therefore, PIII may preferentially induce anti-osteoporosis response by attenuating osteoclastic differentiation and by upregulating NO.

• Nutrition Research and Practice
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• v.11 no.1
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• pp.43-50
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• 2017

BACKGROUND/OBJECTIVES: The present study investigated the hypothesis that a highly pure linear ${\beta}$-1,3-glucan produced by Agrobacterium sp. R259 enhances human natural killer (NK) cell activity and suppresses pro-inflammatory cytokines. SUBJECTS/METHODS: In an eight-week, double-blind, randomized, placebo-controlled clinical trial, 83 healthy adults with white blood cell counts of $4,000-8,000cells/{\mu}L$ were participated and randomly assigned to take two capsules per day containing either 350 mg ${\beta}$-1,3-glucan or placebo. Six participants withdrew their study consent or were excluded due to NK cell activity levels outside the normal range. NK cell activity and serum levels of immunoglobulin G (IgG) and cytokines, such as interferon (IFN)-${\gamma}$, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-${\alpha}$ were measured. RESULTS: NK cell activity and the serum levels of IL-10 were significantly higher from baseline to week 8 in the ${\beta}$-glucan group compared with the placebo group (P = 0.048, P = 0.029). Consumption of ${\beta}$-1,3-glucan also significantly increased NK cell activity compared with placebo after adjusting for smoking and stress status (P = 0.009). In particular, the effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants with severe stress than in those experiencing mild stress. However, the administration ${\beta}$-1,3-glucan did not significantly modulate the levels of IFN-${\gamma}$, IL-2, IL-4, IL-6, IL-12, TNF-${\alpha}$ and IgG compared with the placebo. CONCLUSION: The results showed that supplementation with bacterial ${\beta}$-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.

• Journal of Sasang Constitutional Medicine
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• v.12 no.1
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• pp.186-200
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• 2000

The purpose of this research was to investigate the effects of Indongdeungjikolpitang water extract(IJTE) on the complication of diabetes. IJTE did not affect the level of blood glucose in alloxan- or streptozotocin-induced hyperglycemic mice, but inhibited the motility of gastrointestine. IJTE inhibited the writhing syndrome induced by acetic acid, the permeability of evans blue into peritoneal cavity induced by acetic acid, the paw edema induced by histamine, and the formation of cotton pellet granuloma. IJTE increased the cell viability of thymocytes and splenocytes. IJTE decreased the release of ${\gamma}-interferone$(${\gamma}-IFN$) and interleukin-2(IL-2), but did not affect the release of interleukin-4(IL-4) from murine thymocytes. IJTE increased the release of IL-4 and decreased the release of tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$) and $interleukin-1{\beta}$($IL-1{\beta}$), but did not affect of ${\gamma}-IFN$ and IL-2 from murine splenocytes. IJTE decreased the release of $TNF-{\alpha}$ and $IL-1{\beta}$ from murine peritoneal macrophages. IJTE decreased the production of niric oxide(NO) from murine peritioneal macrophages and increased the phagocytic activity of murine peritoneal macrophages. These results suggest that IJTE has an anti-inflammatory action via the inhibition of $TNF-{\alpha}$, $IL-1{\beta}$ and NO production from immune cells.

• The korean journal of orthodontics
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• v.39 no.4
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• pp.248-256
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• 2009

Objective: The aim of this study was to determine if human PDL cells can produce osteoclastogenic mRNA and examine how compressive stress affects the expression of osteoclastogenic mRNA in human PDL cells. Methods: Human PDL cells were obtained from biscupids extracted for orthodontic treatment. The compressive force was adjusted by increasing the number of cover glasses. PDL cells were subjected to a compressive force of 0.5, 1.0, 2.0, 3.0 or $4.0\;g/cm^2$ for 0.5, 1.5, 6, 24 or 48 hours. Reverse transcription polymerase chain reaction (RT-PCR) analysis was performed to examine levels of M-CSF, IL-$1{\beta}$, RANKL, OPG mRNA expression. Results: Human PDL cells could produce M-CSF mRNA. Human PDL cells under compressive stress showed increased M-CSF, IL-$1{\beta}$ and RANKL mRNAs expression in a force (up to $2\;g/cm^2$) and time-dependent manner. However, OPG mRNA expression was constant regardless of the level and duration of stress. Conclusions: Continuous compressive stress induced the mRNA expression of osteoclastogenic cytokines including M-CSF, RANKL, IL-$1{\beta}$ in PDL cells. Together with an unchanged OPG mRNA level, these results suggest that compressive stress-induced osteoclastogenesis in vivo is partly controlled by M-CSF, RANKL and IL-$1{\beta}$ expression in PDL cells.