• 대한한의학회지
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• 제21권3호
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• pp.20-30
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• 2000

Objective : This experiment was performed in order to study the effect of an aqueous extract of Salviae radix root(SRRAE) on NO production and NOS gene induction from macrophages Methods : To investigate dose-dependent effects of SRRAE for NO release on the $rIFN-{\gamma}-treated$ macrophages, the cells were incubated for 6 hrs in a medium containing $rIFN-{\gamma}$ (5 U/ml), stimulated with SRRAE and incubated in a CO2 incubator. The cells were treated with 5 U/ml $rIFN-{\gamma}$ plus 100 g/ml of SRRAE, Then, the cells were incubated with various concentrations of NGMMA at $37^{\circ}C$ for 48 hrs, Results : SRRAE had no effect on NO production by itself, whereas recombinant $interferon-{\gamma}(rIFN-{\gamma})$ alone showed modest activity, When SRRAE was used in combination with $rIFN-{\gamma}$, there was a marked cooperative induction of NO production in a dose-dependent manner. The optimal effect of SRRAE on NO production was shown at 6hrs after treatment with $rIFN-{\gamma}$. The SRRAE-induced production of NO was inhibited by NG-monomethyl- L-arginine(NGMMA) and arginase. $rIFN-{\gamma}$ in combination with SRRAE showed a marked increase of the expression of the inducible NOS(iNOS) gene. In addition, the effect of SRRAE was mainly dependent on the SRRAE-induced tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ secretion. Conclusions : SRRAE induces NO production from macrophages as a result of SRRAE-induced $TNF-{\alpha}$ secretion. SRRAE may provide a second signal for synergistic induction of NO production in macrophages already induced to express iNOS gene by $rIFN-{\gamma}$.

• Journal of Microbiology and Biotechnology
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• 제12권6호
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• pp.916-920
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• 2002

This report describes a high-level expression of human alpha-2a interferon ($IFN{\alpha}-2a$) in Escherichia coli and its pilot scale purification by using a monoclonal antibody-independent chromatographic procedure that is based on anion-exchange, cation-exchange, hydrophobic interaction, and gel filtration. The recombinant E. coli produced much more $IFN{\alpha}-2a$ in a soluble form, when cultivated at low temperatures than at high-temperature fermentation. However, if the bacterial growth was taken into consideration, fermentation at $30^{\circ}C$ seemed optimal for the interferon production. By using our new protocol, we recovered approximately 160 mg of $IFN{\alpha}-2a$ with a specific activity of $3.59{\times}10^8$ IU/mg from 201 of the broth. The gel permeation chromatographic and SDS-PAGE indicated that the interferon preparation was purified to homogeneity and was of the correctly folded fast-migrating monomer.

• 한국식품영양과학회지
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• 제29권2호
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• pp.342-348
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• 2000

In this experiment, we show the effects of herbal plant extracts on the production of nitric oxide (NO) and TNF-$\alpha$. The extracts of Angelica gigas, Astragalus membranaceus, Acanthopanax sessiliflorus and Houttuynia cordata had no effect on NO synthesis by itself in mouse macrophage cell line (RAW264.7). However, the stimulation with these extracts in the presence of murine interferon-${\gamma}$(mIFN-${\gamma}$) resulted in increased NO synthesis. When these extracts were used in combination with mIFN-${\gamma}$, there were a marked cooperative induction of NO and TNF-$\alpha$ synthesis in a dose-dependent manner. The same results were obtained in the mouse peritoneal macrophages used. The optimal concentration of these extracts on NO synthesis was shown at 100$\mu\textrm{g}$/mL with 100U/mL of mIFN-${\gamma}$. NO synthesis was inhibited by NG-monomethyl-L-arginine. When cell lines were treated with extracts, the expression of inducible NO synthetase (iNOS) was markedly increased in RT-PCR analysis. In addition, synergy between mIFN-${\gamma}$ and extracts was dependent on extracts-induced tumor necrosis factor-$\alpha$(TNF-$\alpha$). These results suggest that water extracts of herbal plants can induce iNOS, NO and TNF-$\alpha$ synthesis of mouse macrophage cell line (RAW264.7) and peritoneal macrophages in combination with mIFN-${\gamma}$.

• Clinical and Experimental Pediatrics
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• 제63권2호
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• pp.52-55
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• 2020

Background: Immunomodulatory properties of interferon (IFN) have been documented. It may induce autoimmune diseases such as autoimmune thyroiditis with hypo- or hyperthyroidism. In addition, it may impair thyroid hormone synthesis through affecting iodide organification in thyroid gland. Purpose: The aim of this study was to describe thyroid function tests disturbances in children with chronic hepatitis C (CHC) receiving pegylated interferon-alpha (PEG IFN-α) plus ribavirin. Methods: Fifty children with CHC virus infection who received combined pegylated interferon-alpha with ribavirin were selected. Other 50 apparently healthy children of matched age and sex (considered as control group) were selected. All children (100) were subject to liver function tests, virological studies, and follow-up of thyroid function test during and after the treatment course. Results: Our study showed that 28% of children received combined PEG IFN-α plus ribavirin showed subclinical hypothyroidism. After 24 weeks treatment with combined therapy of IFN plus ribavirin, the mean level of thyroid stimulating hormone (TSH) was 3.23±88 mU/mL, while TSH was 1.16±0.77 mU/mL before starting treatment. On the other hand, mean TSH was 1.09±0.92 mU/mL in normal control group. Conclusion: This study revealed an association between subclinical thyroid dysfunction and treatment with IFN-alpha and ribavirin in children. Further studies on larger number of patients and longer follow-up duration are recommended for further confirmation.

• Journal of Pharmaceutical Investigation
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• 제16권3호
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• pp.118-123
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• 1986

Time-concentration curves of recombinant human interferon alpha$(rIFN-{\alpha}A)$ in the skin and serum of nude mice or rats were studied after topical application of IFN ointment. IFN appeared in the skin and serum in less than 30 minutes and lasted for more than 10-12 hours at high concentration level after the application to nude mice at a dose of $9.0{\times}10^5\;IU/g$ mouse. But in the rats, IFN was not detected in the serum even 7 hours after the application at a dose of $6.0{\times}10^5\;IU/g$ rat. Topical application of IFN might be useful for the topical and systemic treatment if the human skin resembles that of nude mouse in respect to transport characteristics.

• Journal of Yeungnam Medical Science
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• 제15권2호
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• pp.237-245
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• 1998

만성 B형 간염 환자에서 Interferon (IFN) 치료 후 혈청 HBeAg 소실 및 anti-HBe의 양전율을 높이고 효율적인 치료의 근거를 알기 위하여 치료 전 간기능검사상 갑자기 상승한 혈청 ALT치를 나타낸 환자군과 그렇지 않은 대조군을 대상으로 하여 IFN을 투여한 군과 IFN 치료없이 정상 HBeAg의 자연 소실을 보인 환자군을 임상적으로 장기간 관찰하고 조사하였다. ALT치가 정상 상한치의 4배 이상 높이 증가되어 3개월 이상 왕복을 보인 40명의 환자(A군)와 ALT치가 정상 상한치의 3배 이하로 증가된 10명(B군)에게 ${\alpha}$-IFN 2b를 매일 300만 단위 피하주사로 3~12개월 주사하였다. 대조군으로는 ALT치가 A군처럼 장승한 45명 (C군)이었으며, IFN 치료없이 평균 2.9년을 관찰하였다. HBeAg/anti-HBe 혈청 양전율은 A군 68%, B군 20%, C군 13%이었으며 IFN 치료 중단 후 1년까지의 HBeAg 재양성율은 A군에서 29%였고 HBeAg이 소실된 A와 B군의 38명중에서 6명에서 HBV DNA가 양성이었다. 6명중 4명은 HBeAg/anti-HBe 양전을 보였으나 HBV DNA 양성이었고 나머지 2명은 HBeAg, anti-HBe 및 HBV DNA (hybridization) 모두 음성이었으나 중합효소연쇄반응검사상 HBV DNA 양성이었다. 이상의 결과를 보면 비록 IFN 치료 후에 HBeAg이 소실되었다가 다시 양성화되더라도 IFN은 단기간내에 혈중 HBeAg이나 DNA가 자연적으로 감소가 될 환자나 그렇지 않은 환자에게도 HBV의 비증식화를 유발하여 도움이 될 것으로 사료된다. 그러나 IFN 투여 후에도 혈중 HBeAg과 DNA 소실에 전혀 도움이 되지 않을 환자 및 HBV 증식 억제효과가 기대되는 HBV 간질환 환자의 조건, IFN 투여량, 기간 등에 대한 계획적이고 체계적인 연구로 더 나은 치료효과를 기대할 수 있으리라 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제52권5호
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• pp.497-505
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• 2002

연구배경 : 결핵의 방어면역에서 IFN-${\gamma}$는 매우 중요한 역할을 한다. IFN-${\gamma}$ 수용체의 완전결손이 있는 환자는 Mycobacterium 감염에 감수성이 높아서 매우 치명 적이다. 매우 드문 일부 Mycobacterium 감염에서 IFN-${\gamma}$ 수용체의 완전결손 외에 여러 종류의 부분결손들과 STAT1의 돌연변이들이 알려져 있다. 특히, IFN-${\gamma}$ 수용체의 부분결손이 있는 환자들의 경우 병리학적 소견파 임상적 경과가 일반적 결핵과 유사한 소견을 보이는 것으로 알려져 있다. 방 법 : 임상적 결핵환자에서 IFN-${\gamma}$ 수용체의 기능을 평가하여 대조군과 비교하였다. IFN-${\gamma}$ 수용체의 이상이 있을 가능성이 가장 높은 파종성 결핵환자의 DNA에서 앞서 발표된 증례들에서 확인된 IFN-${\gamma}$ 수용제와 STAT1의 유전적 이상을 확인하였다. 결 과 : 말초혈액 단핵구를 recombinant IFN-${\gamma}$ (100, 1000IU/ml)로 자극하였을 때 대조군과 환자군에 모두 HLA-DR과 CD64의 발현이 증가하였으나, 두 군간의 차이는 없었다. 대조군과 환자군에서 모두 LPS자극하였을 때 TNF-${\alpha}$의 생산이 증가하였으며 IFN-${\gamma}$로 전처치 후에 다시 LPS로 자극하였을 때 TNF-${\alpha}$의 생산은 더욱 더 증가하였다. 그러나, 두 군간의 통계적으로 유의한 차이는 없었다. 파종성 결핵 환자에서 기존에 알려진 IFNgR1과 STAT1의 돌연 변이를 확인하였을 때 특이한 이상소견을 발견할 수 없었다. 결 론 : 임상적 결핵에서 IFN-${\gamma}$ 수용체의 기능적 및 유전적 이상을 확인할 수 없었다. 기존의 연구에서 BCG와 NTM 감염과 관련 있는 것으로 알려진 IFN-${\gamma}$수용체의 이상 만으로는 임상적 결핵의 개체감수성을 설명할 수 없었다.

• BMB Reports
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• 제29권6호
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• pp.530-534
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• 1996

Astrocyte are the major glial cell type in the central nervous system (CNS), and analogous to macrophage, mediates the number of immune responses such as production of cytokines including tumor necrosis factor alpha ($TNF-{\alpha}$) upon activation. $TNF-{\alpha}$ has been implicated in neuroimmunological disorders through killing oligodendrocytes and thus causing demyelination. It has been previously demonstrated that mitogen-activated T cells synthesized a 26 kDa precursor form of $TNF-{\alpha}$ which is bound to the surface of a membrane, and is later secreted as a 17 kDa mature version. In order to examine whether astrocytes would produce the transmembrane form of $TNF-{\alpha}$, astrocytes were stimulated with biological stimuli and the membrane form of $TNF-{\alpha}$ was analyzed by Western blot and FACS analysis. When astrocytes are stimulated with lipopolysaccharide (LPS), $IFN-{\gamma}/LPS$, or $IFN-{\gamma}/IL-1{\beta}$, they were able to express a membrane-anchored $TNF-{\alpha}$ of approximately 26 kDa protein which was immunoreactive to an $anti-TNF-{\alpha}$ antibody, whereas unstimulated astrocytes or astrocytes treated with $IFN-{\gamma}$ or $IL-1{\beta}$ alone was not. Our FACS data were also consistent with the immunoblot analysis. Our result suggests that the membrane form of $TNF-{\alpha}$ expressed by activated astrocytes may cause local damage to oligodendrocytes by direct cell-cell contact and contribute to demyelination observed in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE).

• 대한한의학회지
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• 제19권2호
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• pp.36-49
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• 1998

HERBA SAURURI (HS) has been known to use antiinflammatory drug. To investigated the mechanism of HS-induced NO synthesis, I evaluated the ability of protein kinase C (PKC) inhibitors such as staurosporine (STSN) or polyymyxin B to block HS-induced effects. HS alone had only a small effect, whereas in combination with $rIFN-{\gamma}$, markedly increased NO synthesis in a dose dependent manner. STSN and polymyxin B decreased NO synthesis, which had been induced by $rIFN-{\gamma}$, plus HS. Furthermore, prolonged incubation of the cells with phorbol ester, which down-regulates PKC activity abolished synergistic cooperative effect of HS with $rIFN-{\gamma}$ on NO synthesis. STSN and Polymyxin B potently inhibited HS-induced $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. However, $rIFN-{\gamma}$ plus $TNF-{\alpha}-induced$ NO synthesis was not blocked by STSN or polymyxin B. On the other hand, tyrosine kinase inhibitor, genistein, blocked the NO synthesis and $TNF-{\alpha}$ secretion by $rIFN-{\gamma}$ plus HS. In conlusion, the present results strongly suggest that the capacity of HS to increase NO synthesis from $rIFN-{\gamma}-primed$ macrophages is the result of HS-induced $TNF-{\alpha}$ secretion via the signal transduction pathway of PKC and tyrosine kinase.

• 한국균학회지
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• 제27권3호통권90호
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• pp.237-241
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• 1999

잔나비걸상 Elfvingia applananta 자실체의 수용성성분 EA의 varicella zoster virus(Oka strain; VZV/oka)에 대한 항바이러스효과를 plaque reduction assay에 따라 실험한 결과 EA는 용량의존적으로 plaque 형성을 억제하였으며 $EC_{50}$는 $464.14\;{\mu}g/ml$이었다. EA와 단백질성 항바이러스제인 interferon(IFN) alpha 및 IFN gamma와의 병용시험 결과, 단독처리시와 병용처리시에 m(slope) value가 서로 유사한 값을 보였으므로 이들은 상호 배타적인 약물(mutually exclusive drug)임을 알 수 있었고, IFN alpha와의 병용시 combination index(CI)는 f(a)가 0.50에서 0.90인 유효농도 범위내에서 $0.83{\sim}1.09$의 값을 나타내어 부분적 상승 또는 상가효과를 보였으며, IFN gamma와의 병용시에는 $1.20{\sim}1.24$를 나타내어 길항효과를 보였으므로, IFN alpha와의 병용이 IFN gamma와의 병용보다 더 우수한 병용효과를 나타내었다.