• 대한한의학방제학회지
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• 제16권2호
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• pp.155-162
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• 2008

Objectives : The present study was designed to investigate corelation between mix proportion of Scutellaria baicalensis (SB) and Coptis chinensis (CC) on lipopolysaccharide (LPS)-induced TYPE-1 interferon production. Methods : I examined TYPE-1 interferon, interferon regulating factor (IRF)-1,7 and interleukin(IL)-10 production on LPS-induced RAW264.7 cells to evaluate inhibitory effect of mix proportion of SB and CC using real time PCR. Results : Mixture of SB and CC regulated TYPE-1 interferon and IRF-1,7 mRNA expression with SB dose dependent manner, while maintained IL-10 mRNA expression on LPS-induced RAW264.7 cells. Conclusion : In mixture of SB and CC, SB plays a key role in reducing TYPE-1 interferon through inactivation IRF-1,7. Furthermore mixture of SB and CC maintained IL-10 mRNA level. Collectively, this results suggest that SB confer beneficial effects in autoimmune diseases clinically.

• 대한한의학방제학회지
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• 제16권2호
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• pp.219-228
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• 2008

Objective : The present study was designed to investigate whether the water extract of the root of Scutellaria baicalensis could regulate lipopolysaccharide (LPS)-induced type 1 interferon. Methods : To evaluate of type 1 interferon inhibitory effect of the root of Scutellaria baicalensis, we examined type 1 interferon in LPS-stimulated RAW264.7 cells. Furthermore, Interleukin (IL)-10 and interferon regulatory factor (IRF) - 1, 7 expression level were examined to study the inhibition mechanisms. Results 1. Extract from the root of Scutellaria baicalensis didn't have any cytotoxity itelf. 2. Extract from the root of Scutellaria baicalensis inhibited interferon-a,b in dose dependant- and type 1 interferon production in time dependant manner. 3. Extract from the root of Scutellaria baicalensis reduced IL-10 and IRF-1, 7 production in LPS-stimulated RAW 264.7 cells. Conclusion : The extract from the root of Scutellaria baicalensis down-regulated LPS-induced type 1 interferon through suppression of IL-10 and IRF-1, 7 expression. This results suggested that the extract from the root of Scutellaria baicalensis may be a beneficial drug against inflammatory diseases.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제1권1호
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• pp.79-89
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• 1998

목 적: 만성 B형 간염 환자의 치료에 많은 항바이러스제와 면역조절 물질이 시도되었지만 현재까지는 ${\alpha}$-interferon만이 일정한 효과가 있는 것으로 보고되고 있다. 또 면역조절제 중에는 현재thymodulin 등의 면역증강 물질이 시도되어지고 있다. 저자들은 interferon 치료시 thymodulin을 병용하면 소아의 B형 만성 활동성 간염에 interferon 단독 치료보다 효과가 있는지를 조사해 보았다. 대상 및 방법: 1990년 3월부터 1996년 2월까지 경북대학교병원 소아과에 입원하였던 환아 중 6개월 이상 HBsAg과 HBeAg 및 HBV DNA가 양성(1+~4+)이고, 혈청 AST와 ALT치가 상승되어 있으며 간조직 검사상 만성 활동성 간염으로 확진된 환아 23명($9.8{\pm}2.8$세)을 대상으로 recombinant ${\alpha}$-interferon 300 MU($280\;MU/m^2{\pm}68$; 범위: $189{\sim}448\;MU/m^2$)를 주 3회씩 6개월간 피하 주사하였다. 그 중 10명에게는 thymodulin 60 mg을 매일 복용시켰고 13명은 ${\alpha}$-interferon만 투여하였으며 치료 종료 후 최소 12개월 이상 추적 검사를 하였다. 양군간의 모든 변수에서 통계학적 유의차는 없었다. 결 과: 1) 23명 전예에서 interferon 치료 중에 AST, ALT 및 HBV DNA의 감소가 있었고 12개월째 추적 검사상 9명(39%)에서 평균 3.1개월째에 HBeAg과 anti-HBe의 혈청전환 및 HBV DNA의 음전이 생겼으며 18개월째 추적검사에서는 이 중 2명에서 ${\alpha}$-interferon 중단 후 8개월과 9개월에 HBeAg이 다시 나타났고 또 다른 2명에서 추가로 혈청전환이 생겨서 전체적으로는 23명의 환아 중 11명(48%)에서 혈청전환이 생겼고 재발한 2명을 빼면 최종 성적은 9명(39%)이 된다. 2) 수직 감염이 있는 7례 중 2례(29%)에서 혈청 전환이 생긴 반면 수직 감염이 없는 12례 중 6례(50%)에서 혈청전환이 생겨 수직 감염 유무는 혈청전환과의 상관 관계가 밀접하다고 생각한다. 3) ${\alpha}$-interferon 치료 전의 ALT치가 정상치의 2배 이하인 경우 8례 중 3례(38%)에서 혈청전환이 있었는데 비해 2배 이상이었던 경우는 15예 중 8례(53%)에서 혈청전환이 있어서 ${\alpha}$-interferon 치료전의 높은 ALT치가 좋은 치료 효과를 예측하는데 도움이 될 수 있을 것으로 생각한다. 4) ${\alpha}$-interferon 치료 전의 HBV DNA가 3+ 이상이었던 경우는 12례 중 5례(42%)에서 혈청전환이 있었는데 비해 1+ 이었던 경우는 11례 중 6례(55%)에서 혈청전환이 있어서 ${\alpha}$-interferon 치료전의 낮은 HBV DNA가 좋은 치료 효과를 예측하는데 도움이 될 수 있을 것으로 생각한다. 5) B형 만성 활동성 간염 환아 23례 중 10례에게 thymodulin을 병용하여 투여하였으나 10례 중 5례(50%)에서 혈청전환이 있었으며 이는 대조군인 ${\alpha}$-interferon 단독 치료 시의 13례 중 6례(46%)와 비교할 때 통계적인 의의를 찾을 수 없었다. 결 론: 면역조절 물질인 thymodulin의 투여로써 숙주 면역계의 기능을 증강시켜 바이러스의 제거를 촉진하고자 소아의 B형 만성 활동성 간염에 ${\alpha}$-interferon 치료시 thymodulin을 병용하여 치료하였으나 ${\alpha}$-interferon 단독 치료보다 더 효과가 있다고 볼 수는 없었으며 향후 더 많은 환아를 대상으로 한 interferon과 다른 종류의 항바이러스제 및 면역조절제 등과의 병용 치료 연구가 더 좋은 결과를 얻기 위해 필요할 것으로 생각한다.

• KSBB Journal
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• 제6권1호
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• pp.9-14
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• 1991

We studied the production and excretion of alpha-interferon in recombinant Escherichia coli harboring plasmid pIF-III-B, which carries alpha-interferon gene under the control of lipoprotein and lacUV5 promoter, and lac operator. Basically, the effects of concentrations of ampicillin and an inducer, IPTG, for the expression of the cloned gene, on the productions of alpha-interferon and plasmid stability were studied. The highest production of alpha-interferon was observed at 50 mg/1 of ampicillin concentration and 0.5 mM of IPTG. The plasmid pIF-III-B was maintained very stably in medium with ampicillin but segregated rapidly in medium without ampicillin. Also, the plasmid was segregated more rapidly in medium with an inducer higher than 0.5 mM.

• KSBB Journal
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• 제5권3호
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• pp.293-298
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• 1990

대장균의 lipoprotein promoter, lac UV5 promoter 및 operator와 lipoprotein의 signal sequence를 가지는 vector에 alpha-IFN유전자를 cloning함으로써 제작된 plasmid plF-III-B와 plF-III-C를 여러종류의 대장균 숙주 세포에 형질 전환하여 IFN의 생산성을 조사해 본 결과 $lpp^-$형질을 가지는 JE5505가 가장 우수했으며, 기존 plasmid, Hif-2h에 비해 130배 높은 생산성을 보였다. 또한 생산된 IFN의 약 50%가 세포 외부로 분비됨을 확인하였다.

• Journal of Microbiology and Biotechnology
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• 제28권11호
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• pp.1908-1915
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• 2018

Upon viral infection, the host cell recognizes the invasion through a number of pattern recognition receptors. Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) recognize RNA molecules derived from invading viruses, activating down-stream signaling cascades, culminating in the induction of the type I interferon. On the other hand, viruses have evolved to evade type I interferon-mediated inhibition. Hepatitis E virus has been shown to encode a few antagonists of type I interferon and it is not surprising that viruses encode multiple mechanisms of viral evasion. In the present study, we demonstrated that HEV PCP strongly down-regulates MDA5-mediated activation of interferon ${\beta}$ induction in a dose-dependent manner. Interestingly, MDA5 protein expression was almost completely abolished. In addition, polyinosinic polycytidylic acid (poly(I:C))- and Sendai virus-mediated activation of type I interferon responses were similarly abrogated in the presence of HEV PCP. Furthermore, HEV PCP down-regulates several molecules that play critical roles in the induction of type I IFN expression. Taken together, these data collectively suggest that HEV-encoded PCP is a strong antagonist of type I interferon.

• Journal of Microbiology and Biotechnology
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• 제27권10호
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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 $interferon-{\gamma}$.

• 대한한방내과학회지
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• 제26권1호
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• pp.74-92
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• 2005

Objectives/Methods : To analyze the effect of Injinchunggantang(IJCGT) to Interferon-${\alpha}/{\beta}$ signal transmission system in HepG2 cells, HepG2 Cell were treated with IJCGT. Also, revelation of MxA, 2'5'-OAS mRNA leaded by Interferon-${\alpha}/{\beta}$ and revelation and activation of Jak1, TYK1, and STAT 1, all main signal transmission factors, were analyzed. Results : The analysis resulted in the following 1. With interferon ${\alpha}/{\beta}$ there was no affect cell propagation of Hep G2 cells. With IJCGT alone, cell propagation of HepG2 was promoted, and cell propagation control function was recovered. 2. With interferon ${\alpha}/{\beta}$ cell death was unaffected. With IJCGT apoptosis of HepG2 cell was restrained, and the cell's reaction to interferon was unaffected. 3. With interferon ${\alpha}/{\beta}$ treatment mRNA revelation of MxA and 2'5'-OAS was induced. When HepG2 cells were injected with IJCGT without interferon ${\alpha}/{\beta}$ treatment, mRNA revelation of MxA and 2'5'-OAS increased in proportion to the treatment density. With pre-treatment of IJCGT, leaded with interferon ${\alpha}/{\beta}$, promoted revelation of MxA, 2'5' -OAS mRNA. 4. Though mRNA revelation of lakl, TYK1 and STAT1 was unaffected with IJCGT, activation of STAT1 was promoted with an increase of phosphorylation of STAT1 protein. With pre-treatment of IJCGT, Jak1, TYK2, STAT1 phosphorylation, leaded with interferon, strengthened. 5. TNF-a, IL-1b and LPS present, revelation of MxA and 2'5'-OAS mRNA leaded by interferon was restrained when HepG2 cells were treated with IJCGT, and the interferon signal transmission system restraint action leaded by inflammatory cytokines was moderated. Conclusion : These results support a role for IJGCT in promotion of anti-virus action through maintainance of the liver's sensibility toward interferon. A clinical study of an interferon treated patient treated also with IJGCT is needed to determine its efficacy.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제3권1호
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• pp.56-62
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• 2000

목 적: 만성 B형 간염 환자의 치료에 interferon alfa는 효과가 있는 것으로 알려지고 있지만 연구자에 따라 차이가 있으며 소아에서의 치료 후의 조직학적 변화에 대한 연구는 거의 없는 실정이다. 저자들은 소아 만성 B형 간염에서 interferon alfa의 치료 효과와 추적 생검이 가능했던 환자에서의 조직학적 변화에 대해 알아보고자 하였다. 대상 및 방법: 1995년 3월부터 1997년 8월까지 서울대학교병원 소아과에서 6개월 이상 HBsAg과 HBeAg 및 HBV DNA가 양성이었으며 간 조직검사상 만성 간염으로 확진된 환자 35명을 대상으로 recombinant interferon alfa 3~6 MU(평균 $3.4\;MU/m^2$)를 주 3회씩 6개월간 피하주사 하였다. 치료 시작 12개월 이상 혈청학적 변화를 추적 관찰하였다. interferon에 반응이 있는 환자 중 18명에서 치료후 간생검을 실시하여 조직학적 변화를 분석하였다. 결 과: 1) 치료 환자 35명 중 17명(49%)에서 인터페론 치료 시작 6개월에 HBV DNA의 감소가 있었고, 12개월째에 22명(63%)에서 HBeAg 및 HBV DNA의 음전이 생겼으며 18개월까지는 25명(71%)에서 관찰되었다. 반응군에서 혈청 ALT치는 모두 정상화되었고, HBsAg의 음전은 1명에서 관찰되었다. 2) 어머니가 HBsAg 보유자가 아닌 수평감염, 치료전 ALT가 정상의 2배 이상, 간조직의 심한 괴사와 염증이 interferon에 대한 반응이 좋은 예측인자이었다. 3) 치료 후 반응군의 간조직 소견에서 간맥주위괴사, 소엽내 활성도, 간맥내 염증, 간섬유화, total HAI가 유의하게 감소하였다. 결 론: 소아 만성 B형 간염에서 interferon alfa 치료 후 63%에서 반응을 보였으며, 혈청학적 변화는 조직학적 소견의 호전과 연관이 있다. 소아 만성B형 간염 환아에서 interferon 치료는 혈청학적, 생화학적, 조직학적 관해를 유도하는 효과적이고 안전한 치료방법이다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권4호
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• pp.1681-1684
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• 2014

Objective: To investigate interferon (IFN) alpha 2 b for treating patients with JAK2V617F positive polycythemia vera (PV) and essential thrombocytosis (ET). Methods: Interferon alpha 2 b was used to treat patients with JAK2V617F positive PV and ET. In control group, hydroxyurea was used. Endpoint of study was to compare rates of hematological and molecular remission. Results: Patients in the interferon alpha 2 b group achieved higher rates of hematologic and molecular remission than patients in the hydroxyurea group, with a lower incidence of thrombosis. Conclusion: Compared with hydroxyurea, interferon alpha 2 b could reduce JAK2V617F load for patients with PV and ET, and achieve higher molecular remission, improve treatment efficacy and reduce complications.