• Journal of Korean Society for Atmospheric Environment
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• 제18권E2호
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• pp.121-128
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• 2002

This study was carried out to investigate if nitric oxide synthase (NOS) inhibitors modulate airway inflammation induced by diesel exhaust particles (DEP). N$\^$G/-nitro-L-arginine methyl ester (L-NAME), a potent constitutive NOS (cNOS) inhibitor, and aminoguanidine (AG), a selective inducible NOS (iNOS) inhibitor, were administered to mice in their drinking water for 7 weeks. Airway inflammation was elicited by the repeated intratracheal administration of DEP. The results showed that macrophages, inflammatory eosinophils and neutrophils in bronchoalveolar lavage (BAL) fluids by intratracheal DEP instillation were significantly suppressed in the mice treated with two NOS inhibitors toghther with DEP. The suppression of these cells was more effective in AG treated groups than in L -NAME treated groups. NOS inhibitor treatment also reduced interleukin -5 (IL-5 in the BAL fluids and lung homogenates. Additionally, it was found that eosinophil peroxidase (EPO) activity in the BAL fluids was also decreased by NOS inhibitor treatment. These results suggest that nitric oxide (NO) is produced in airway inflammation by repeated DEP instillation, and that iNOS inhibition as well as cNOS inhibition can play a modulating role in this airway inflammation by DEP.

• Archives of Plastic Surgery
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• 제38권4호
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• pp.351-358
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• 2011

Purpose: The inflammatory phase is considered an integral part of adult wound healing, but fetal wound healing studies have shown scarless healing results in the absence of the inflammation process. The COX-2 pathway is an essential component of inflammation. The purpose of this study is to identify the effect of a topical selective COX-2 inhibitor on inflammation in rabbit skin wound healing and scarring. Methods: Full-thickness wounds were made on 6 New Zealand rabbits' ears. Topical 5% celecoxib + vehicle (experimental tissue) and vehicle only (controlled tissue) were applied daily for 14d on each side of the ears. Scar samples were harvested at 2 wks, 4 wks, and 8 wks after the wounding. Each sample was stained with hematoxylin and eosin and the Masson's trichrome stain to evaluate inflammation and scar formation. Results: Histological analysis demonstrated a significant reduction of inflammation, neovascularization, and scar elevation in the experimental tissue as compared to the control. Additionally, experimental tissue exhibited faster improvement of collagen organization similar to that of normal tissue. Conclusion: This study suggests that the topical application of a selective COX-2 inhibitor on a rabbit ear wound resulted in decreased inflammation and had a positive effect on the reduction of scar formation.

• Molecules and Cells
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• 제20권2호
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• pp.167-172
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• 2005

Ceruloplasmin (Cp) is a copper protein with important functions in iron homeostasis and in inflammation. Cp mRNA expression is induced by interferon (IFN)-${\gamma}$ in U937 monocytic cells, but synthesis of Cp protein is halted after about 12 h by transcript-specific translational silencing. The silencing mechanism requires binding of a 4-component cytosolic inhibitor complex, IFN-gamma-activated inhibitor of translation (GAIT), to a defined structural element (GAIT element) in the Cp 3'-UTR. Translational silencing of Cp mRNA requires the essential proteins of mRNA circularization, suggesting that the translational inhibition requires end-to-end mRNA closure. These studies describe a new mechanism of translational control, and may shed light on the role that macrophage-derived Cp plays at the intersection of iron homeostasis and inflammation.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 추계학술대회
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• pp.31-31
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• 2018

Benign prostatic hyperplasia (BPH), which is the most common disorder in elderly men, involves androgenic hormone imbalance with chronic inflammation that causes imbalance between cell apoptosis and cell proliferation. As the root cause of the BPH remains unclear and synthetic drugs for treatment of BPH have undesirable side effects, the development of effective alternative medicines has been considered. Chinese Skullcap has been considered natural remedy to treat pyrexia, micturition disorder and inflammation. Although skullcap has effective properties on various diseases, the effects and molecular mechanism of Skullcap on BPH are not fully understood. Therefore, in this study, we evaluated the efficacy of Chinese Skullcap root extract (SRE) in testosterone-induced BPH rats. Compared with the untreated group, the SRE treatment group suppressed pathological alterations, such as prostate growth and increase in serum dihydrotestosterone and $5{\alpha}$-reductase levels. Furthermore, SRE significantly decreased the expression of androgen receptor and proliferating cell nuclear antigen. SRE also restored Bax/Bcl-2 balance. These effect of SRE was more prevalent than commercial $5{\alpha}$-reductase inhibitor, finasteride. Taken together, we propose that SRE suppresses abnormal androgen events in prostate tissue and inhibits the development of BPH by targeting inflammation- and apoptosis-related markers. These finding strengthens that SRE could be used as plant-based $5{\alpha}$-reductase inhibitory alternative.

• International Journal of Oral Biology
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• 제41권3호
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• pp.125-131
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• 2016

The aim of the present study was to develop an animal model for evaluation of temporomandibular (TMJ) nociception under TMJ inflammation. We also investigated the participation of $IL-1{\beta}$ in inflammation-induced TMJ nociception. Experiments were carried out using male Sprague-Dawley rats. Intra-articular injection of 3% formalin was administered to evaluate hyperalgesia 3 days after CFA injection. Intra-articular injection of 3% formalin did not produce nociceptive behavior in normal rats. Although intra-articular injection of 3 doses of CFA produced TMJ inflammation, only 1:3 diluted CFA produced hyperalgesia when formalin was injected intra-articularly 3 days after CFA injection. Co-administration of IL-1 receptor inhibitor with formalin into the TMJ cavity 3 days after CFA injection was performed. Co-administration of IL-1 receptor inhibitor significantly inhibited formalin-induced hyperalgesia in rats with CFA-induced TMJ inflammation. These results suggested that intra-articular injection of formalin produced hyperalgesia under chronic TMJ inflammation. Moreover, $IL-1{\beta}$ plays an important role in TMJ hyperalgesia under chronic inflammation and blockade of $IL-1{\beta}$ is a potential therapeutic target for inflammatory TMJ pain.

• Molecules and Cells
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• 제27권4호
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• pp.417-422
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• 2009

Lipoxygenase (LO) metabolites are generated in inflamed tissues. However, it is unclear whether the inhibition of the LO activity regulates the expression of c-Fos protein, a pain marker in the spinal cord. Here we used a carrageenan-induced inflammation model to examine the role of LO in the development of c-Fos expression. Intradermally injected carrageenan caused elevated number of cells exhibiting Fos-like immunoreactivity (Fos-LI) in the spinal dorsal horn, and decreased the thermal and mechanical threshold in Hargreaves and von Frey tests. Pretreatment with an inhibitor of phospholipase A2, that generates the LO substrate, prior to the carrageenan injection significantly reduced the number of Fos-(+) cells. A general LO inhibitor NDGA, a 5-LO inhibitor AA-861 and a 12-LO inhibitor baicalein also exhibited the similar effects. Moreover, the LO inhibitors suppressed carrageenan-induced thermal and mechanical hyperalgesic behaviors, which inidcates that the changes in Fos expression correlates with those in the nociceptive behaviors in the inflamed rats. LO products are endogenous TRPV1 activators and pretreatment with BCTC, a TRPV1 antagonist inhibited the thermal but not the mechanical hypersensitivity. Overall, our results from the Fos-LI and behavior tests suggest that LO products released from inflamed tissues contribute to nociception during carrageenan-induced inflammation, indicating that the LO pathway is a possible target for modulating inflammatory pain.

• Journal of Life Science
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• 제9권2호
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• pp.5-8
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• 1999

We isolated a sphingonyelinase (SMase) inhibitor, which would be a potential reagent to regulate cell proliferation, oncogenesis, and inflammation, from a strain of Streptomyces sp.. In this paper, we report the optimal conditions for the production of SMase inhibitor, designed as sphinin, from Streptomyces sp. F50970. The optimal carbon and nitrogen source were 1% soluble starch and 0.05%-0.15% trypton. Most of monosaccharides and high concentration of soluble starch above 1.0% caused falling of pH and sphinin production. Zn2+, Cu2+, Fe2+, Mn2+, and Co2+inhibited cell growth and the production of sphinin. Inorganic phosphate promoted the sphinin production. Optimal initial pH for the production of sphinin was 7.5-8.0. Addition of CaCO3 to the medium resulted in an increase of inhibitor production. Based on these results, we designed a fermentation medium for the production of a SMase inhibitor, sphinin, from Streptomyces sp. F50970.

• BMB Reports
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• 제50권11호
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• pp.584-589
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• 2017

Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-${\alpha}$, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-${\alpha}$. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ${\kappa}B$ ($I{\kappa}B$)-kinase ${\beta}$ ($IKK{\beta}$) at Ser177/181. This dephosphorylation led to the stabilization of $I{\kappa}B{\alpha}$ and inhibition of NF-${\kappa}B$ activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-$IKK{\beta}$ and inhibiting NF-${\kappa}B$ signaling.

• Journal of Periodontal and Implant Science
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• 제40권1호
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• pp.33-38
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• 2010

Purpose: The purpose of this study was to observe and quantify the expression of interleukin-4 (IL-4), interferon-$\gamma$ (IFN-$\gamma$), and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the gingival tissue of patients with type 2 diabetes mellitus (DM) and healthy adults with chronic periodontitis. Methods: Twelve patients with type 2 DM and chronic periodontitis (Group 3), twelve patients with chronic periodontitis (Group 2), and twelve healthy individuals (Group 1) were included in the study. Clinical criteria of gingival (sulcus bleeding index value, probing depths) and radiographic evidences of bone resorption were divided into three groups. The concentrations of cytokines were determined by a western blot analysis and compared using one-way ANOVA followed by Tukey's test. Results: The expression levels of IFN-$\gamma$ and TIMP-2 showed an increasing tendency in Groups 2 and 3 when compared to Group 1. On the other hand, the expression of IL-4 was highest in Group 1. Conclusions: The findings suggest that IFN-$\gamma$ and TIMP-2 may be involved in the periodontal inflammation associated with type 2 DM. IL-4 may be involved in the retrogression of the periodontal inflammation associated with type 2 DM.

• Journal of Applied Biological Chemistry
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• 제66권
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• pp.1-6
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• 2023

Dendranthema zawadskii is a one of the popular plants as native in South Korea. In this study, linarin was isolated and purified using silica-gel, Diaion, and Sephadex LH-20 from the aerial parts of D. zawadskii. The chemical structure was completely identified through spectroscopic data including 1D, 2D nucleic magnetic resonance, and HRFABMS. Furthermore, linarin inhibited the bacterial neuraminidase (BNA) activity with 13.5 μM of IC₅₀ dose-dependently. Through the enzyme kinetic experiments, linarin as BNA inhibitor exhibited a typical noncompetitive inhibition mode which K_m was contestant and V_max decreased as the concentration of the inhibitor increased. It was further identified that the inhibition constant was 16.0 μM. Linarin was the most abundance metabolite in the aerial part of D. zawadskii extract by UHPLC-TOF/MS analysis. Therefore, D. zawadskii and its main component are expected that it can be effectively used for the infection and inflammation caused by bacteria.