• 제목, 요약, 키워드: $interferon{\gamma}$

검색결과 536건 처리시간 0.044초

Specific Expression of Interferon-γ Induced by Synergistic Activation Mediator-Derived Systems Activates Innate Immunity and Inhibits Tumorigenesis

  • Liu, Shuai;Yu, Xiao;Wang, Qiankun;Liu, Zhepeng;Xiao, Qiaoqiao;Hou, Panpan;Hu, Ying;Hou, Wei;Yang, Zhanqiu;Guo, Deyin;Chen, Shuliang
    • Journal of Microbiology and Biotechnology
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    • v.27 no.10
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    • pp.1855-1866
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    • 2017
  • The synergistic activation mediator (SAM) system can robustly activate endogenous gene expression by a single-guide RNA. This transcriptional modulation has been shown to enhance gene promoter activity and leads to epigenetic changes. Human $interferon-{\gamma}$ is a common natural glycoprotein involved in antiviral effects and inhibition of cancer cell growth. Large quantities of high-purity $interferon-{\gamma}$ are important for medical research and clinical therapy. To investigate the possibility of employing the SAM system to enhance endogenous human $interferon-{\gamma}$ with normal function in innate immunity, we designed 10 single-guide RNAs that target 200 bp upstream of the transcription start sites of the $interferon-{\gamma}$ genome, which could significantly activate the $interferon-{\gamma}$ promoter reporter. We confirmed that the system can effectively and highly activate $interferon-{\gamma}$ expression in several humanized cell lines. Moreover, we found that the $interferon-{\gamma}$ induced by the SAM system could inhibit tumorigenesis. Taken together, our results reveal that the SAM system can modulate epigenetic traits of non-immune cells through activating $interferon-{\gamma}$ expression and triggering JAK-STAT signaling pathways. Thus, this strategy could offer a novel approach to inhibit tumorigenesis without using exogenous $interferon-{\gamma}$.

$Interferon-\gamma$가 치주인대 세포의 Collagen 및 Fibronectin의 합성과 Alkaline Phosphatase 활성에 미치는 영향 (EFFECTS OF $INTERFERON-\gamma$ ON COLLAGEN AND FIBRONECTIN SYNTHESIS IN PRIMARY CULTURED PERIODONTAL LIGAMENT CELLS)

  • 김광석;성재현;최제용;류현모
    • 대한치과교정학회지
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    • v.23 no.2
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    • pp.229-248
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    • 1993
  • 결합 조직의 대사를 억제하고, 골조직이나 골세포의 골기질 대사 역시 억제하는 것으로 알려져 있는 $Interferon-\gamma(IFN-\gamma)$의 교정치료에의 이용 가능성을 평가하기 위하여, 교정력에 의한 골 개조 과정에서 중심적 역할을 하는 것으로 알려진 치주인대 세포를 primary culture하여 배양된 세포에 $IFN-\gamma$를 투여함으로써 이것이 골조직 기질의 합성능에 미치는 영향에 대하여 관찰하였다. $IFN-\gamma$는 세포의 DNA합성능을 약하게 증가시켰으며, 세포내 DNA 총량에는 영향을 미치지 않았다. 따라서 이 실험에서 사용한 용량의 $IFN-\gamma$는 세포에 독성이 없다고 할 수 있으며, 다른 결합조직 세포에서 나타나는 항증식 효과와는 반대되는 결과였다. $IFN-\gamma$는 비교원성 단백질(NCP)의 합성을 증가시키는 양상을 나타내었으나, 교원질(CDP)의 합성은 감소시키는 경향을 보여, 총단백질에 대한 교원질의 합성비율은 $IFN-\gamma$에 의해 용량 의존적으로 감소하였다. 또한 교원질의 mRNA양은 단백질 합성과 유관하게 $IFN-\gamma$에 의해 억제되었다. 따라서 $IFN-\gamma$는 교원질 합성의 전사과정 혹은 그 이후의 과정에 영향을 미칠 것으로 예상할 수 있다. 한편 Indomethacin의 투여로 $IFN-\gamma$에 의해 억제된 교원질의 합성이 영향을 받지 않았기 때문에 $IFN-\gamma$에 의한 교원질 합성 과정에 prostaglandin이 관련되지 않았음을 알 수 있었다. 반면 fibronectin의 합성은 10 및 100 U/ml의 $IFN-\gamma$ 투여시에는 영향을 받지 않았으나, 1000U/ml의 $IFN-\gamma$투여시에는 유의한 증가를 나타내어, 교원질에서와는 다른 영향을 나타내었다. 또한 mRNA steady state level에서도 $IFN-\gamma$는 교원질의에서와는 달리 fibronectin mRNA 양에는 영향을 미치지 않았다. 즉 $IFN-\gamma$ fibronectin 유전자 발현에 영향을 미치는 부위는 전사나, 전사후 변형단계가 아닌 단백질 합성단계에서 영향을 미침을 보여주었다. 따라서 $IFN-\gamma$ 교원질과 fibronectin합성 조절 영향을 미치는 부위 서로 다름을 알 수 있겠다. Alkaline phospatase의 활성은 10-1000 U/ml의 $IFN-\gamma$를 투여시 약하게 증가시키는 경향을 보였으나 석회화가 일어날 정도로 높게 증가시키지는 못했다. 따라서 $IFN-\gamma$는 골기질의 주성분인 type I 교원질의 합성을 선택적으로 억제하는 기능과 alkaline phosphatase의 활성을 크게 증가시키지 못한 점 등으로 미루어 볼 때, 골개조를 억제하는 방향으로 작용한다고 볼 수 있으며, 교정치료 과정중 골개조를 억제하는 부위에서 사용을 시도해 볼 수 있겠다.

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인터페론감마에 의한 A549 폐암세포주 세포독성의 기전 (The Mechanism of Interferon-$\gamma$ Induced Cytotoxicity on the Lung Cancer Cell Line, A549)

  • 오연목;유철규;정화순;김영환;한성구;심영수
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.1
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    • pp.63-68
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    • 1996
  • 연구배경: 인터페론감마-(interferon-$\gamma$)는 항바이러스 효과, 암세포의 형증식 효과, 대식세포 및 B 림프구의 활성화, 주면역복합체(MHC) 항원 발현의 증가 등의 생물학적 효과를 나타낸다. 특히, 인터페론감마의 항암 효과는 이미 생체 내외에서 입증되어 실제 폐암 환자에 대한 임상 연구가 시도되고 있다. 그러나, 인터페론감마의 항암효과 기전은 여러가지 가설이 제시되기는 하고 있지만 아직 확립된 것이 없다. 세포의 괴사(necrosis)는 심한 외부의 스트레스에 의해서 발생하는 세포 사망의 형태로 잘 알려져 있다. 생명현상 중 괴사와는 전혀 다른 세포 사망의 과정으로 아포프토시스(apoptosis)가 있다. 아포프토시스는 조직의 항상성(homeostasis of tissue volume), 개체의 발생과정, 장기의 퇴행(regression), tolerance 등의 여러 생명 활동 과정에서 발생하는 세포 사망의 과정으로서, 세포질 및 핵이 분절화(fragmentation)되어 죽어가는 능동적 사망과정으로 알려져 있다. 아포프토시스에서는 수동적으로 죽어가는 괴사에서 볼 수 없는 DNA 분절화(DNA ladder pattern)가 특징적으로 관찰된다. 인터페론감마의 암세포에 대한 세포독성 기전을 연구하기 위해서 인터페론감마를 폐암세포주인 A549세 처치한 후 현미경(inverted microscope)로 A549의 변화를 관찰하였는데 A549세포가 분절화되면서 죽어가는 것을 관찰할 수 있었다. 저자들은 인터페론감마의 항암기전으로서 아포프토시스의 가능성을 평가하고자 본 연구를 시행하였다. 방법: 폐암세포주인 A549세포를 대상으로 하였다. A549세포에 여러 농도의 인터페론감마를 투여하고 24시간, 72시간, 120시간 후에 MTT(dimethylthiazolyl diphenyltetrazolium bromide) bioassay법으로 세포독성을 정량화하였다. 그리고, 100 unit/ml의 인터페론감마를 A549 세포에 120시간 처치 후, 광학 현미경으로 세포 사망의 양상을 관찰하였다. 또한, 100 unit/ml의 인터페론감마를 투여하고 120시간이 경과한 후 사망 세포의 DNA를 추출하여 1.5% agarose gel에서 전기 영동을 시행하고 ethidium bromide로 염색 후 DNA ladder pattern 유무를 관찰하였다. 결과: 1) 인터페론감마에 의한 A549 폐암세포주의 세포독성 효과는 24시간에는 거의 없다가 72시간부터 120시간 사이에 나타나기 시작하여 120시간에는 더 증가하였다. 2) 인터페론감마에 의한 A549 세포의 사망 양상은 광학현미경상 A549 세포들이 작은 분절로 나뉘면서 사망하였다. 3) 인터페론감마를 A549 폐암세포주에 처치 후 죽어기는 세포의 DNA를 추출하여 전기영동시킨 결과 아포프토시스(apoptosis)에서 특징적으로 보이는 DNA ladder pattern을 관찰할 수 있었다. 결론: 인터페론감마(interferon-$\gamma$)의 A549 폐암세포주에 대한 세포독성의 기전은 아포프토시스 과정을 통해서 일어난다.

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닭 인터페론 유전자의 클로닝에 관한 연구 (MOLECULAR CLONING OF CHICKEN INTERFERON-GAMMA)

  • 송기덕;;한재용
    • 한국가금학회:학술대회논문집
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    • pp.34-50
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    • 1999
  • A cDNA encoding chicken interferon-gamma (chIFN-${\gamma}$) was amplified from P34, a CD4$^{+}$ T-cell hybridoma by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into pUC18. THe sequences of cloned PCR products were determined to confirm the correct cloning. Using this cDNA as probe, chicken genomic library from White Leghorn spleen was screened. Phage clones harboring chicken interferon-gamma (chIFN-${\gamma}$) were isolated and their genomic structure elucidated. The chIFN-${\gamma}$ contains 4 exons and 3 introns spanning over 14 kb, and follows the GT/AG rule for correct splicing at the exon/intron boundaries. The four exons encode 41, 26, 57 and 40 amino acids, respectively, suggesting that the overall structure of IFN-${\gamma}$ is evolutionairly conserved in mammalian and avian species. The 5’-untranslated region and signal sequences are located in exon 1. Several AT-rich sequences located in the fourth exon may indicate a role in mRNA turnover. The 5’-flanking region contains sequences homologous to the potential binding sites for the mammalian transcription factors, activator protein-1(AP-1) activator protein-2(AP-2) cAMP-response element binding protein(CREB), activating transcription factor(ATF), GATA-binding fator(GATA), upstream stimulating factor(USF), This suggests that the mechanisms underlying transcriptional regulation of chicken and mammalian IFN-${\gamma}$ genes may be similar.r.

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체외 Interferon-gamma 검사를 이용한 결핵감염의 진단 (Diagnosis of Mycobacterium tuberculosis Infection using Ex-vivo interferon-gamma Assay)

  • 이정연;심태선
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.5
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    • pp.497-509
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    • 2006
  • Until recently, the tuberculin skin test (TST) has been the only tool available for diagnosing a latent TB infection. However, the development of new diagnostic tools, using the Mycobacterium tuberculosis (MTB)-specific early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) antigens, should improve the control of tuberculosis (TB) by allowing a more accurate identification of a latent TB infection (LTBI). Antigen-specific interferon-gamma ($IFN-{\gamma}$) assays have greater specificity in BCG-vaccinated individuals, and as less biased by nontuberculous mycobacterial infections. Many comparative studies have suggested that those assays have a higher specificity than the TST, and the sensitivity of these assays are expected to remarkably improved if more MTB-specific antigens can become available. Nevertheless, the major obstacle to the widespread use of these tests is the limited financial resources. Similar to other diagnostic tests, the predictive value of $IFN-{\gamma}$ assays depends on the prevalence of a MTB infection in the population being tested. Therefore, prospective studies will be meeded to establish the applicability of these new assays at multiple geographic locations among patients of different ethnicities, and to determine if the $IFN-{\gamma}$ responses can indicate those with a high risk of progressing to active TB.

감마 인터페론, LBD-001의 Adjuvant 관절염 억제작용 및 기타 일반 약리작용 (Inhibitory Effect on Adjuvant Arthritis and Other Pharmacological Profile of Gamma-Interferon, LBD-001)

  • 이은방;김제현;김운자;김정근
    • 약학회지
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    • v.34 no.3
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    • pp.171-179
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    • 1990
  • The recombinant gamma-interferon (LBD-001) which was produced by yeast as host system was investigated on the pharmacological activities. This gamma-interferon exhibited potent inhibitory effect on adjuvant induced arthritis, but no effect on carrageenin induced paw edema in rats. It did not show any sedative, anticonvulsive, analgesic and hypothermic activities in animals. It also had no influences on isolated tracheal muscle and ileum of guinea pig, isolated uterus and fundus strip of rats, and on blood pressure and respiration in situ experiments of rabbits.

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The Inhibitory Activity of Erigeron annuus-Derived Components on $Interferon-{\gamma}$ and Lipopolysaccharide-Induced Nitric Oxide Production in Mouse Pheritoneal Macrophage

  • Lee, Hee-Jung;Kim, You-Ah;Jeong, Na-Ho;Hong, Seung-Heon;Seo, Young-Wan
    • Journal of Applied Biological Chemistry
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    • v.50 no.3
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    • pp.160-163
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    • 2007
  • Two flavonoids (1 and 2) and one phenolic acid (3) obtained from Erigeron annuus have recently been shown to have potent antioxidant activities. Aim of this study was to investigate the inhibitory effects of these components on $interferon-{\gamma}$ and lipopolysaccharide-induced nitric oxide productions in the mouse pheritoneal macrophage. Compounds 2 and 3 showed marked inhibitory activities against inducible nitric oxide synthase (iNOS) on the lipopolysaccharide and $interferon-{\gamma}-stimulated$ mouse pheritoneal macrophages without cytotoxicity. Therefore, these results suggest that the compounds could be effective anti-inflammatory agents as nitric oxide inhibitors in vivo.

Interferon 및 gamma-globulin이 실험적 Pneumocystis carinii 폐염의 치료에 미치는 영향 (Study on the therapeutic effects of interferon and gamma-globulin in experimental Pneumocustis curinii pneumonia)

  • 신대환;강대영
    • The Korean Journal of Parasitology
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    • v.30 no.3
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    • pp.219-226
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    • 1992
  • This study was performed to observe the therapeutic effects of interferon-gamma ($IFN-{\gamma}$) and gamma-globulin (${\gamma}-globulin$) in experimental Pneumocystis carinii pneumonia of immune suppressed mice. After 9 weeks, trimethoprim-sulfamethoxaBole(TMP-SMZ; 10~50 mg/mouse/day), mouse $IFN-{\gamma}(5{\times}10^4$ units/mouse/day) and mouse ${\gamma}-globulin$(20 mg/mouse/day) were administered to the mice for 3 weeks by the experimental group. The therapeutic efficacy was evaluated by body weights, histopatholo단ic and electron microscopic findings of the lungs, and number of p. carinii cysts by Gomori's methenamine silver stain. Body weights of the mice were significantly increased in the group of combination therapy of TMP-SMZ with $IFN-{\gamma}{\;}or{\;}{\gamma}-globulin$, and in the group of TMP- SMZ treatment(p<0.05), however, little effect was found in the group of T-globulin alone. Histopathologic 6ndings of p. carinii pneumonia were much improved in the group of combination therapy of TMP-SMZ with $IFN-{\gamma}$. Treatment with either TMP-SMZ or $IFN-{\gamma}$ significantly reduced the number of cysts in the p. carinii pneumonia, but {\gamma}-globulin alone was ineffective. In electron microscopic findings of p. carinii pneumonia, the number of trophozoites and cysts were reduced by treatment with either TMP-SMZ or $IFN-{\gamma}$, and most of the cysts were empty or containing one or two intracystic bodies. The present results suggested, that combination therapy of TMP-SMZ with $IFN-{\gamma}$ had synergistic effects in treatment of P carinii pneumonia in experi- mental mice.

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The Poly-γ-ᴅ-Glutamic Acid Capsule of Bacillus licheniformis, a Surrogate of Bacillus anthracis Capsule Induces Interferon-Gamma Production in NK Cells through Interactions with Macrophages

  • Lee, Hae-Ri;Jeon, Jun Ho;Rhie, Gi-Eun
    • Journal of Microbiology and Biotechnology
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    • v.27 no.5
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    • pp.1032-1037
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    • 2017
  • The poly-${\gamma}$-$\small{D}$-glutamic acid (PGA) capsule, a major virulence factor of Bacillus anthracis, provides protection of the bacterium from phagocytosis and allows its unimpeded growth in the host. We investigated crosstalk between murine natural killer (NK) cells and macrophages stimulated with the PGA capsule of Bacillus licheniformis, a surrogate of the B. anthracis capsule. PGA induced interferon-gamma production from NK cells cultured with macrophages. This effect was dependent on macrophage-derived IL-12 and cell-cell contact interaction with macrophages through NK cell receptor NKG2D and its ligand RAE-1. The results showed that PGA could enhance NK cell activation by inducing IL-12 production in macrophages and a contact-dependent crosstalk with macrophages.

Usefulness of interferon-γ release assay for the diagnosis of latent tuberculosis infection in young children

  • Yun, Ki Wook;Kim, Young Kwang;Kim, Hae Ryun;Lee, Mi Kyung;Lim, In Seok
    • Clinical and Experimental Pediatrics
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    • v.59 no.6
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    • pp.256-261
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    • 2016
  • Purpose: Latent tuberculosis infection (LTBI) in young children may progress to severe active tuberculosis (TB) disease and serve as a reservoir for future transmission of TB disease. There are limited data on interferon-${\gamma}$ release assay (IGRA) performance in young children, which our research aims to address by investigating the usefulness of IGRA for the diagnosis of LTBI. Methods: We performed a tuberculin skin test (TST) and IGRA on children who were younger than 18 years and were admitted to Chung-Ang University Hospital during May 2011-June 2015. Blood samples for IGRA were collected, processed, and interpreted according to manufacturer protocol. Results: Among 149 children, 31 (20.8%) and 10 (6.7%) were diagnosed with LTBI and active pulmonary TB, respectively. In subjects lacking contact history with active TB patients, TST and IGRA results were positive in 41.4% (29 of 70) and 12.9% (9 of 70) subjects, respectively. The agreement (kappa) of TST and IGRA was 0.123. The control group, consisting of non-TB-infected subjects, showed no correlation between age and changes in interferon-${\gamma}$ concentration after nil antigen, TB-specific antigen, or mitogen stimulation in IGRAs (P=0.384, P=0.176, and P=0.077, respectively). In serial IGRAs, interferon-${\gamma}$ response to TB antigen increased in IGRA-positive LTBI subjects, but did not change considerably in initially IGRA-negative LTBI or control subjects. Conclusion: The lack of decrease in interferon-${\gamma}$ response in young children indicates that IGRA could be considered for this age group. Serial IGRA tests might accurately diagnose LTBI in children lacking contact history with active TB patients.