• Title/Summary/Keyword: immune-mediated disease

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Induction of Heat Shock Protein 70 Inhibits Tumor Necrosis $Factor{\alpha}-induced$ Lipid Peroxidation in Rat Mesangial Cells (Heat Shock Protein 70이 흰쥐 배양 혈관간 세포에서 관찰되는 $TNF{\alpha}$에 의한 지질과산화에 미치는 보호 효과)

  • Ha, Hun-Joo;Park, Young-Mee;Ahn, Young-Soo;Kim, Kyung-Hwan
    • The Korean Journal of Pharmacology
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    • v.31 no.3
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    • pp.323-331
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    • 1995
  • Monocyte/macrophage infiltration is the well known initial features associated with the development of glomerular disease including non-immune mediated nephropathy. Tumor necrosis factor ${\alpha}(TNF{\alpha})$, a cytokine produced primarily by monocyte/macrophage, exhibits similar effects as observed at the initial stages and during the progression of glomerular injury. Because the mesangial cells are target cells for glomerular injury, the present study examined the effect of $TNF{\alpha}$ on glomerular mesangial cell membrane lipid peroxidation as an index of cytotoxicity attributing to $TNF{\alpha}$. Primary culture of rat mesangial cell was established by incubation of glomeruli isolated from male Sprague-Dawley rat kidneys utilizing a standard sieving method. The levels of lipid peroxides in the mesangial cells were quantitated by malondialdehyde- thiobarbituric acid adduct formation. During an 8 hour incubation at $37^{\circ}C$, $TNF{\alpha}$ at 10 to 10,000 units/ml increased the levels of lipid peroxides dose dependently. Western blot analysis demonstrated that a short thermal stress induced heat shock response and the synthesis of heat shock protein 70(hsp70) in this mesangial cells. Further, this induction of hsp 70 prevented increase of lipid peroxides in the mesangial cells exposed to $TNF{\alpha}$. These data suggest that $TNF{\alpha}-induced$ lipid peroxidation in the mesangial cells may have pathophysiological relevance to glomerular injury and prior induction of heat shock response may play a role in the cellular resistance against $TNF{\alpha}-induced$ glomerular injury.

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The Effects of Corticosteroid Solutions in OLP Patients (구강편평태선에 대한 스테로이드 가글의 효과비교 연구)

  • Jeong, Sung-Hee;Park, Su-Hyeon;Ok, Soo-Min;Huh, Joon-Young;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.37 no.1
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    • pp.27-33
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    • 2012
  • Oral lichen planus(OLP) is a chronic inflammatory disease with cell-mediated immune responses, but the exact cause is unknown. The treatment aim of OLP is not complete cure but to alleviate symptoms. In this study, two kinds of corticosteroid gargling solutions used for comparing the effects. From 2002 to 2010, 180 patients diagnosed with oral lichen planus and received topical steroid therapy in the Pusan National University Dental Hospital. Each of two types of solution contained dexamethasone (dexamethasone disodium phosphate) and prednisolone ($solondo^{(R)}$). A period of relief of symptoms and recurrence was recorded. The group using solution containing dexamethasone(dexa gargle) was prescribed to 33 patients(25 female, 8 male) and another group containing prednisolone (solon gargle) included 147 patients (114 female, 33 male). The effect of dexa gargle seemed faster than the solon gargle. There was no significant difference for recurrent rate between the groups using dexa and solon gargle.

Adequate concentration of B cell leukemia/lymphoma 3 (Bcl3) is required for pluripotency and self-renewal of mouse embryonic stem cells via downregulation of Nanog transcription

  • Kang, Songhwa;Yun, Jisoo;Kim, Da Yeon;Jung, Seok Yun;Kim, Yeon Ju;Park, Ji Hye;Ji, Seung Taek;Jang, Woong Bi;Ha, Jongseong;Kim, Jae Ho;Baek, Sang Hong;Kwon, Sang-Mo
    • BMB Reports
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    • v.51 no.2
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    • pp.92-97
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    • 2018
  • B cell leukemia/lymphoma 3 (Bcl3) plays a pivotal role in immune homeostasis, cellular proliferation, and cell survival, as a co-activator or co-repressor of transcription of the $NF-{\kappa}B$ family. Recently, it was reported that Bcl3 positively regulates pluripotency genes, including Oct4, in mouse embryonic stem cells (mESCs). However, the role of Bcl3 in the maintenance of pluripotency and self-renewal activity is not fully established. Here, we report the dynamic regulation of the proliferation, pluripotency, and self-renewal of mESCs by Bcl3 via an influence on Nanog transcriptional activity. Bcl3 expression is predominantly observed in immature mESCs, but significantly decreased during cell differentiation by LIF depletion and in mESC-derived EBs. Importantly, the knockdown of Bcl3 resulted in the loss of self-renewal ability and decreased cell proliferation. Similarly, the ectopic expression of Bcl3 also resulted in a significant reduction of proliferation, and the self-renewal of mESCs was demonstrated by alkaline phosphatase staining and clonogenic single cell-derived colony assay. We further examined that Bcl3-mediated regulation of Nanog transcriptional activity in mESCs, which indicated that Bcl3 acts as a transcriptional repressor of Nanog expression in mESCs. In conclusion, we demonstrated that a sufficient concentration of Bcl3 in mESCs plays a critical role in the maintenance of pluripotency and the self-renewal of mESCs via the regulation of Nanog transcriptional activity.

Tumorigenic Effects of Endocrine-Disrupting Chemicals are Alleviated by Licorice (Glycyrrhiza glabra) Root Extract through Suppression of AhR Expression in Mammalian Cells

  • Chu, Xiao Ting;Cruz, Joseph Dela;Hwang, Seong Gu;Hong, Heeok
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5117-5121
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    • 2014
  • Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

GENE EXPRESSION ANALYSIS OF THE DENTAL PULP IN HEALTHY AND CARIES TEETH (치아 우식증에 따른 치수내 유전자 발현 변화에 관한 분석)

  • Oh, So-Hee;Kim, Jong-Soo
    • Journal of the korean academy of Pediatric Dentistry
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    • v.37 no.3
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    • pp.275-287
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    • 2010
  • Deep caries may induce pulpitis and the pulpal tissue interacts with microbial invasion. The immune response to protect the pulpal tissue can be mediated by cellular signal molecules produced by the pulpal cells. The understanding of these processes is important to find future therapeutic method for the diseased pulp. The pulp tissue from sound teeth was set as control group (n=30) and the pulp tissue from decayed teeth was set as test group (n=30). Total RNA was extracted from the pulp of each group and it was used for cDNA microarray and reverse transcriptase-polymerase chain reaction(RT-PCR). The expression of TGF-${\beta}1$ was studied by immunohistochemistry. The results were as follows: 1. cDNA microarray analysis identified 520 genes with 6-fold or greater difference in expression level with 143 genes more abundant in health and 377 genes more abundant in disease. 2. The RT-PCR analysis was done for randomly selected 14 genes and the results supported the result of cDNA microarray assay. 3. TGF-${\beta}1$ was highly expressed in the carious pulp and it was found in odontoblast by immunohistochemistry. In conclusion, many cytokines were found to be significantly changed their expression in the diseased pulp(/M/>1.6).

A Sterile Pyogranuloma/Granuloma Syndrome (SPGS) in a Rottweiler Dog (Rottweiller에서 발생한 무균성 농성 육아종성/육아종성 피부증후군(SPGS))

  • Kim Youn-ju;Jeong A-young;Kim Jae-hoon;Eom Ki-dong;Lee Keun-woo;Oh Tae-ho
    • Journal of Veterinary Clinics
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    • v.21 no.4
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    • pp.402-405
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    • 2004
  • A 5-year-old Rottweiler neutered female dog was presented with signs of mandibular and popliteal lymphadenopathy, erosion in mucocutaneous junction of muzzle and lips, multiple papules and nodules in right rear limb and neck, and alopecia in right thorax. There was no further clinical sign except anorexia, sporadic fever and ocular hyperemia. She hadn't shown any response to carprofen prescribed by local veterinarian. Hematological abnormalities included mild anemia and severe lymphocytosis. On serum biochemical profile, only elevated AST level was noticed. On cytological examination, there was an evidence of mild bacterial infection which seemed to occur secondarily. Three sites were biopsied that included muzzle, upper lip and right thoracic region. Histopathologically, multifocal confluent pyogranulomatous dermatitis, scattered granulomatous inflammation in subcutis and severe septal panniculitis were observed. Special stainings(Gram, Acid-fast, PAS, Giemsa) were performed to reveal that a dog was negative for any organism. Finally, sterile pyogranuloma/granuloma syndrome (SPGS) was diagnosed. The treatment was initiated with predinsolone and enrofloxacin. The condition was successfully resolved after 4 weeks of treatment. This good response suggests that SPGS may be immune-mediated disease of its pathogenesis and this drug combination may be a viable therapeutic option for dogs suffering from SPGS. Also, this article reports a case of SPGS in Rottweiller for the first time.

A New Treatment Modality Using Topical Sulfasalazine for Oral Lichen Planus (구강편평태선에 대한 sulfasalzine의 국소적용)

  • Jeong, Sung-Hee;Park, Su-Hyeon;Ok, Soo-Min;Heo, Jun-Young;Ko, Myung-Yun;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.37 no.3
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    • pp.155-159
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    • 2012
  • Background Oral lichen planus (OLP) is a chronic inflammatory disease characterized by cell-mediated immune responses, but the exact cause is unknown. Sulfasalazine has shown efficacy in the treatment of cutaneous lichen planus. Objective Our purpose was to assess the usefulness of sulfasalazine in treatment of OLP resistant to corticosteroid therapy. This study provides a new option for controlling OLP symptoms. Methods Two patients with the symptomatic reticular form of OLP were treated with 30 mg/5 ml of topical sulfasalazine for 8 to 15 weeks and were evaluated for symptom severity using a numerical analog scale during each week of treatment. The lesion size was measured using a 2 $mm^2$ grid. Results After 2 weeks of application, both patients reported improvements in their symptoms and lesions. Most of the lesions disappeared after 8 weeks of treatment without any side effects. Conclusion Topical sulfasalazine can be a successful treatment option for patients with oral lichen planus resistant to steroid therapy.

A Novel Therapeutic Effect of a New Variant of CTLA4-Ig with Four Antennas That Are Terminally Capped with Sialic Acid in the CTLA4 Region

  • Piao, Yongwei;Yun, So Yoon;Kim, Hee Soo;Park, Bo Kyung;Ha, Hae Chan;Fu, Zhicheng;Jang, Ji Min;Back, Moon Jung;Shin, In Chul;Won, Jong Hoon;Kim, Dae Kyong
    • Biomolecules & Therapeutics
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    • v.30 no.6
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    • pp.529-539
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    • 2022
  • Rheumatoid arthritis (RA) is a multifactorial immune-mediated disease, the pathogenesis of which involves different cell types. T-cell activation plays an important role in RA. Therefore, inhibiting T-cell activation is one of the current therapeutic strategies. Cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), also known as abatacept, reduces cytokine secretion by inhibiting T-cell activation. To achieve a homeostatic therapeutic effect, CTLA4-Ig has to be administered repeatedly over several weeks, which limits its applicability in RA treatment. To overcome this limitation, we increased the number of sialic acid-capped antennas by genetically engineering the CTLA4 region to increase the therapeutic effect of CTLA4-Ig. N-acetylglucosaminyltransferase (GnT) and α2,6-sialyltransferase (α2,6-ST) were co-overexpressed in Chinese hamster ovary (CHO) cells to generate a highly sialylated CTLA4-Ig fusion protein, named ST6. The therapeutic and immunogenic effects of ST6 and CTLA4-Ig were compared. ST6 dose-dependently decreased paw edema in a mouse model of collagen-induced arthritis and reduced cytokine levels in a co-culture cell assay in a similar manner to CTLA4-Ig. ST6- and CTLA4-Ig-induced T cell-derived cytokines were examined in CD4 T cells isolated from peripheral blood mononuclear cells after cell killing through irradiation followed by flow- and magnetic-bead-assisted separation. Interestingly, compared to CTLA4-Ig, ST6 was substantially less immunogenic and more stable and durable. Our data suggest that ST6 can serve as a novel, less immunogenic therapeutic strategy for patients with RA.

Prevalence of Combined Bronchial Asthma with COPD in Patients with Moderate to Severe Air flow Limitation (중등증 및 중증의 만성 기류 장애 환자에서 만성폐쇄성폐질환과 기관지 천식의 합병률)

  • Rhee, Yang Keun;In, Byeong Hyun;Lee, Yang Deok;Lee, Yong Chul;Lee, Heung Bum
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.4
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    • pp.386-394
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    • 2003
  • Background : ATS(American Thoracic Society) defined new guidelines for COPD(chronic obstructive lung disease) in April 2001, following the results of the global initiative for chronic obstructive lung disease. The most important concept of COPD is an airflow limitation which is not fully reversible compared to bronchial asthma(BA). The criteria for COPD are postbronchodilator $FEV_1$ less than 80% of the predicted value and an $FEV_1$ per FVC ratio less than 70%. The global initiative for asthma(GINA) study defined asthma, which included immune-mediated chronic airway inflammatory airway disease, and found that airflow limitation was wide spread, variable and often completely reversible. Taken together COPD and BA may be combined in airflow limitation. This study was designed to evaluate the prevalence of BA in patients with COPD of moderate to severe airflow limitation. Methods : COPD was diagnosed by symptoms and spirometry according to ATS guidelines. Enrolled subjects were examined for peak flow meters(PFM), sputum eosinophils and eosinophil cationic protein(ECP) levels, serum total IgE with allergy skin prick test, and methacholine bronchial provocation test(MBPT). Results : About 27% of COPD patients with moderate to severe airflow limitation were combined with BA. There was significantly decreased response to PFM in severe COPD. However, there was no significant relationship between BA and COPD according to the degree of severity. The BA combined with COPD group showed significantly high eosinophil counts and ECP level in induced sputum. However, neutrophil counts in induced sputum showed significant elevation in the pure COPD group. Conclusion : Twenty-seven percent of COPD patients with moderate to severe ventilation disorder were combined with BA, but there were no significant differences according to the degree of severity.

Inhibitory Effects of Anthocyanins Isolated from Black Soybean (Glycine max L.) Seed Coat on Degranulation and Cytokine Generation in RBL-2H3 Cells (검정콩 껍질 유래 안토시아닌의 RBL-2H3 세포에서 탈과립화와 사이토카인 생성 저해 효과)

  • Chung, Mi-Ja;Ha, Tae-Joung;Choi, Ha-Na;Lee, Ji-Sun;Park, Yong-Il
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.12
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    • pp.1662-1667
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    • 2011
  • Anthocyanins belong to a group of flavonoid compounds and are well known for their various health beneficial effects, which include antioxidative activities. Among them, the major anthocyanins isolated from seed coat of black soybean (Glycine max L.) were previously characterized as glycosides containing glucopyranose. Asthma is an allergic disease that is strongly associated with various immune cells, including basophils and mast cells. Eosinophils, basophils, and mast cells play important roles in allergic asthma through the release of inflammatory mediators such as asthma-specific T-helper 2 (Th2) cytokines and subsequent amplification of asthma symptoms via degranulation. Rat basophilic leukemia RBL-2H3 cells are the most common in vitro models for evaluating allergic reactions. In this study, we examined the effects of anthocyanin from seed coat of black soybean on antigen-stimulated degranulation and Th2 cytokine production in RBL-2H3 cells. Cell degranulation was evaluated by measuring the release of ${\beta}$-hexosaminidase. ${\beta}$-Hexosaminidase release and Th2 cytokine production in RBL-2H3 cells was much higher upon stimulation with IgE-antigen complex than those in untreated control cells. Anthocyanins significantly suppressed IgE-antigen complex-induced degranulation of RBL-2H3 cells and inhibited IgE-antigen complex-mediated interleukin (IL)-4, IL-13, and tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) production in RBL-2H3 cells. These findings suggest that anthocyanins from seed coat of black soybean effectively inhibit allergic reactions and may have beneficial effects against allergic asthma.