• Molecular & Cellular Toxicology
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• 제5권3호
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• pp.187-192
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• 2009

Toll-like receptors (TLRs) play an important role in host defense by sensing invading microbial pathogens. The stimulation of TLRs by microbial components triggers the activation of the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon-$\beta$ (TRIF)-dependent downstream signaling pathways. TLR/MyD88 signaling pathway induces the activation of nuclear factor-kappa B (NF-${\kappa}B$) and the expression of inflammatory cytokine genes, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-12, and IL-$1{\beta}$. On the other hand, TLR/TRIF signaling pathway induces the delayed-activation of NF-${\kappa}B$ and interferon regulatory factor 3 (IRF3), and the expression of type I interferons (IFNs) and IFN-inducible genes. The divalent heavy metal cadmium (Cd) is clearly toxic to most mammalian organ systems, especially the immune system. Yet, the underlying toxic mechanism(s) remain unclear. Cd inhibits the MyD88-dependent pathway by ceasing the activity of inhibitor-${\kappa}B$ kinase. However, it is not known whether Cd inhibits the TRIF-dependent pathway. Presently, Cd inhibited NF-${\kappa}B$ and IRF3 activation induced by lipopolysaccharide (LPS) and polyinosinic-polycytidylic acid. Cd inhibited LPS-induced IRF3 phosphorylation and IFN-inducible genes such as interferon inducible protein-10 and regulated on activation normal T-cell expressed and secreted (RANTES). These results suggest that Cd can modulate TRIF-dependent signaling pathways of TLRs.

• Tuberculosis and Respiratory Diseases
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• 제68권3호
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• pp.155-161
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• 2010

Background: The tuberculin skin test (TST) has limitations in diagnosing a latent tuberculosis infection (LTBI). The interferon-gamma release assay (IGRA) was introduced to middle- and high-school students since 2009 by the Korea Centers for Disease Control and Prevention. The aim was to evaluate the utility of IGRA in diagnosing LTBI in middle- and high-school students. Methods: From August 2007 to July 2009, among suspected LTBI students showing TST induration with a 10 mm diameter and over with a normal chest x-ray in school students of Jeju city, 341 students underwent a Quanti FERON-TB Gold In-Tube (QFT-IT) test to confirm LTBI. Results: From 348 students showing a positive TST, a QFT-IT test was carried out on 341 students. The positive QFT-IT rate was 52.8% (=180/341). The positive QFT-IT rate was higher in high-school boys with a 15~19 mm diameter of induration in TST. Conclusion: With the introduction of IGRA for diagnosing LTBI in middle- and high-school students, approximately 47% of students who show a TST induration with a 10 mm diameter and over can avoid taking unnecessary preventive chemotherapy. These results suggest that IGRA is useful for diagnosing and controlling LTBI in Korean students.

• 대한한의학방제학회지
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• 제11권1호
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• pp.115-128
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• 2003

Bojungikgitang is the water extracts prepared from Ginseng Radix, Astragali Radix, Angelicae gigantis Radix, Astractylodis Rhizoma alba, Aurantii nobilis Pericarpium, Glycyrrhizae Radix, Bupleuri Radix, Cimicifugae Rhizoma, which has been used for the treatment of indigestion, and immunological disease in oriental countries. In this study, the effects of Bojungikgitang on the productions of nitiric oxide (NO) and prostaglandin $E_2\;(PGE_2)$, and the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were examined using RAW 264.7 macrophages activated with $interferon-{\gamma}\;(IFN-{\gamma})$ plus lipopolysaccharide (LPS). Bojungikgitang (10-400 ${\mu}$g/ml) per se had no cytotoxic effect in unstimulated macrophages, but this compound dose-dependently reduced the release of NO and $PGE_2$ caused by stimulation of $LPS/IFN-{\gamma}$. The levels of iNOS and COX-2 protein were markedly suppressed by the treatment with Bojungikgitang in a concentration dependent manner. Moreover, Bojungikgitang also attenuated the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (1L)-1${\beta}$ and IL-6 in LPS-stimulated RAW 264.7 macrophages. These results suggest that Bojungikgitang decreases the NO and $PGE_2$ production in macrophages by inhibiting iNOS and COX-2 expression and these properties may contribute to the anti-inflammatory activity of Bojungikgitang.

• 한국동물생명공학회지
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• 제34권4호
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• pp.292-299
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• 2019

Interferon tau (IFNT) regulation, an anti-luteolytic factor produced by conceptuses of the ruminant ungulates, is essential for the maintenance of early pregnancy, but a definitive mechanism for its temporal transcription has not been elucidated. We and others have observed the T-box protein eomesodermin (EOMES) exhibited high mRNA expression in the ovine embryonic trophectoderm; thus, both caudal-relatedhomeobox-2 (CDX2) and EOMES coexist during the early stages of conceptus development. Objective of this study was to examine the effect of EOMES on ovine IFNT gene transcription when evaluated with CDX2, ETS2 and AP1 transcription factors implicated in the control of cell differentiation in the trophectoderm. In this study, quantitatively via reverse transcription-polymerase chain reaction (RT-PCR) analysis between ovine trophoblast cells was initially performed, finding that transcription factors CDX2 and 'EOMES transcription factor mRNAs' were specific to trophectoderm cells. These mRNAs were also found in days 15, 17, and 21 ovine conceptuses. Furthermore, human choriocarcinoma JEG3 cells (trophoblast cell line) were cotransfected with an ovine IFNT (-654bp)-luciferase reporter (-654-oIFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with CDX2, ETS2 and AP1 increased transcription of -654-oIFNT-Luc by about 11-fold compared with transfection of the construct alone. When cells were initially transfected with EOMES followed by transfection with CDX2, ETS2 and/or AP1, the expression of -654-oIFNT-Luc was decreased. Also, EOMES factor inhibited the stimulatory activity of CDX2 alone. These results suggest that when conceptuses attach to the uterine epithelium, ovine IFNT gene transcription is down-regulated by an increase of EOMES factor expression in the attached ovine trophoblast cells.

• 한국미생물·생명공학회지
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• 제14권3호
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• pp.219-223
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• 1986

사람 선유아세포 인터페론의 정제에 사용되는 단 clone성 항체생산 세포주를 조작하기 위하여 BA-LB/C mouse의 복강과 꼬리정맥을 통하여 HuIFN-$\beta$를 면역화시키고 그 비장세포(spleen cells) 와 NS-O 세포주를 세포융합 시켰다. 융합된 1300 hybrids를 ELISA방법으로 선별하고 soft agarose 방법과 limiting dilution방법으로 subcloning하여 높은 항체를 생성하는 것으로 판명된 11 hybrids를 재선별 하였다. 재선별된 11 hybrids 각각의 항체형 (Ig type)을 조사하고 최종 Protein A-sepharose와 친화성이 높은 IgG 2a/형의 clone # 4-1-19와 clone # 551-4-1을 선별하여 배양된 세포를 각각 nude(nu/nu) mouse 및 BALB/c mouse 복강에 접종배양 하였다. 이들 mouse복강액으로 부터 얻은 ascites fluid를 protein A-sepharose를 이용한 affinity column분획으로 항체를 정제하였으며 ascites fluid $m{\ell}$당 약 4mg의 정제된 항체를 얻을 수 있었고 SDS-polyacrylamide gel상에서 전기영동 시킨 결과 분자량 14-16만 dalton으로 추정되는 항체를 확인할 수 있었다.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.297-300
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• 1996

LBD-001, a recombinant human interferon $\gamma$ produced by genetically engineered yeast as a host system, was administered intraperitoneally to Sprague-Dawley male rats from premating to mating period at least for 60 days and to female rats from at least for 2 weeks before mating to early gestation period (from day 0 to 7 of gestation) at dose levels of $0.35\times10^6, 0.39\times10^6, and 1.38\times10^6$ I.U./kg/day. In the positive control group, ethynylestradiol ($EE_2$; 40 $\mu\textrm{g}$/kg/day) was subcutaneously administered only to female rats during the early gestation period. Effects of the test agents on reproductive performances of the male or female rats and embryonic development were as followings; (1) No significant changes by the treatment of LBD-001 were observed in general behaviors, body weight, food and water consumption, and necropsy of parent animals. However, significant decreases of body weight, food consumption, and water consumption were observed in ($EE_2$ -treated female rats. (2) Mating performances and fertility of parent animals were not significantly affected by the treatment of LBD-001. In ($EE_2$ -treated females, however, the fertility was completely inhibited. (3) No changes in resorption rate and external abnormality of F1 fetuses were observed by the treatment of LBD-001. The results show that LBD-001 at the dose of $1.38\times10^6$ I.U./kg/day or less does not affect general toxicity and reproductive function of parent animals and embryonic development of F1 fetuses.

• Biomolecules & Therapeutics
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• 제4권4호
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• pp.301-309
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• 1996

LBD-001, a recombinant human interferon ${\gamma}$ produced by genetically engineered yeast as a host system, was intravenously administered to pregnant female rats (Sprague-Dawley) from day 7 to 17 of gestation at dose levels of 0.35$\times$10$^{6}$ , 0.69$\times$10$^{6}$ , and 1.38$\times$10$^{6}$ I.U./kg/day. As the control groups, hydrocortisone sodium succinate (5 or 10 mg/kg/day) was also similarly administered. Teratological effects of the test agents on fetuses and development of offsprings (F1 rats) were investigated. (1) No significant changes by the treatment of LBD-001 were observed in body weight, food and water consumption, feeding and nursing behaviors, and autopsy of pregnant or lactating mother rats. However, in hydrocortisone sodium succinate (10 mg/kg/day)-treated group, significant decreases of body weight on day 16, 18, and 20 of gestation and food consumption on day 20 of gestation and outstanding atrophy of thymus and adrenals were observed in two rats autopsied on day 20 of gestation. (2) No significant changes in resorption rate, skeletal or visceral development of fetuses, and physical or sensory development of offsprings (Fl) by the treatment of LBD-001 were detected. In hydrocortisone sodium succinate (10 mg/kg/day)-treated group, however, there were significant decreases of body weight of fetuses, delay of ossification, temporary delay of body weights of offsprings (F1) on day 1 and 3 of lactation, and increased tendency of stillborn rate and malformation rate of bone. The results show that LBD-001 at the dose of 1.38$\times$10$^{6}$ I.U./kg/day or less is not teratogenic in organogenesis of fetuses and the development of offsprings (F1). Meanwhile, hydrocortisone sodium succinate (10 mg/kg/day) seems to delay ossification of fetuses and temporarily retard the development of offsprings (Fl).

• 대한수의학회지
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• 제40권1호
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• pp.166-172
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• 2000

Prior to a clinical trial, the in vitro and in vivo antitumor effects of a new recombinant human interferon ${\alpha}-2a$ (rHu/IFN ${\alpha}-2a$) with/without hydroxyurea (HU) were investigated using chronic myelogenous leukemia (CML)-derived cell lines (K562 and KU812F) and BALB/c nude. mice transplanted with KU812F cells. The rHu/IFN ${\alpha}-2a$ ($10^4-10^6IU/ml$) strongly inhibited proliferation of both cell lines and the combined treatments with HU ($10{\mu}g/ml$) were more effective. In nude mice transplanted with KU812F cells. rHu/IFN ${\alpha}-2a(1{\times}10^6IU$) inhibited tumor growth by 42-65% at 15-21 days post-transplantation (DPT). The combined treatment of rHu/IFN ${\alpha}-2a (5{\times}10^5IU$) with HU (0.25mg/g b.w.) inhibited the tumor growth by 48-67% at 12-21 DPT. In addition, the treatment of rHu/IFN ${\alpha}-2a$ ($5{\times}10^6IU\;or\;1{\times}10^7IU$) rejected tumor transplantation by 40%. These results suggest that the new rHU/IFN ${\alpha}-2a$ alone or with HU is effective on CML cell lines.

• 대한한의학회지
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• 제20권1호
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• pp.75-83
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• 1999

To investigate the effects of negative therapy at back meridian points on blood gas components and immune functions in male college students, this study was conducted on treatment types(abdomen group and back group) at three sampling times (before, post-2 wks and post-4 wks) by using $2{\times}3$ factoral design. Blood gas $components(pH,\;PCO_2,\;PO_2,\;HCO_3^-,\;O_2SAT,\;BE)$, red blood cell, hematocrit, hemoglobin, white blood cell and subsets(neutrophil, basophil, eosinophil. lymphocyte, monocyte), total T cells, helper T cells, suppressor T cells, Th/Ts ratio, total B cells, serum immunoglobulin levels (IgG, IgA, IgM, IgD, IgE), Cytokines(Interlukin$-1{\beta}$, -2, -4, 2 receptor, -6 and ${\gamma}$-interferon), NK cells were measured. Collected with data were analyzed statistically by repealed measured ANOVA. The pattern of change between two groups for hematocrit, hemoglobin, suppressor T cells, interleukin-6, ${\gamma}-interferon$, NK cells at post-2 weeks and BE, lymphocyte, basophil at post-4 weeks was significantly different(p<0.05) And also the pattern of change over time for ${HCO_3}^-$(2 wks vs 4 wks), WBC, neutrophil, lymphocyte(0 wks vs 2 wks and 2 wks vs 4 wks) was significantly different(p<0.05). In summary, these data suggest that negative therapy at back meridian points had an effect on blood gas components and immune functions in male college students because practicing negative therapy at back meridian points was not associated with changes of all blood gas components and immune factors but associated with changes of BE, hematocrit, hemoglobin, WBC. neutrophil, lymphocyte, interleukin-6. ${\gamma}-interferon$, NK cells.

• Tuberculosis and Respiratory Diseases
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• 제81권1호
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• pp.59-72
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• 2018

Background: It remains uncertain if $interferon-{\gamma}$ release assays (IGRAs) are superior to the tuberculin skin test (TST) for the diagnosis of active tuberculosis (TB) or latent tuberculosis infection (LTBI) in immunosuppressed populations including people with human immunodeficiency virus (HIV) infection. The purpose of this study was to systematically review the performance of IGRAs and the TST in people with HIV with active TB or LTBI in low and high prevalence TB countries. Methods: We searched the MEDLINE database from 1966 through to January 2017 for studies that compared results of the TST with either the commercial QuantiFERON-TB Gold in Tube (QFTGT) assay or previous assay versions, the T-SPOT.TB assay or in-house IGRAs. Data were summarized by TB prevalence. Tests for concordance and differences in proportions were undertaken as appropriate. The variation in study methodology was appraised. Results: Thirty-two studies including 4,856 HIV subjects met the search criteria. Fourteen studies compared the tests in subjects with LTBI in low TB prevalence settings. The QFTGT had a similar rate of reactivity to the TST, although the first-generation version of that assay was reactive more commonly. IGRAs were more frequently positive than the TST in HIV infected subjects with active TB. There was considerable study methodology and population heterogeneity, and generally low concordance between tests. Both the TST and IGRAs were affected by CD4 T-cell immunodeficiency. Conclusion: Our review of comparative data does not provide robust evidence to support the assertion that the IGRAs are superior to the TST when used in HIV infected subjects to diagnose either active TB or LTBI.