• Archives of Pharmacal Research
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• 제28권5호
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• pp.582-586
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• 2005

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in pro- inflammatory cy tokine induced pain behaviors. Intrathecal injection of tumor necrosis factor-a (TNF-${\alpha}$; 100 pg), interleukin-1${\beta}$ (IL-1${\beta}$ 100 pg) and interferon-${\gamma}$ (INF-${\gamma}$; 100 pg) showed pain behavior. Intrathecal pretreatment with CTX (0.05, 0.1 and 0.5 mg) attenuated pain behavior induced by TNF-${\alpha}$ and INF-${\gamma}$ administered intrathecally. But intrathecal pretreatment with CTX (0.05, 0.1 and 0.5${\mu}g$) did not attenuate pain behavior induced by IL-1${\beta}$. On the other hand, intrathecal pretreatment with PTX further increased the pain behavior induced by TNF-${\alpha}$ and IL-1${\beta}$ administered intrathecally, especially at the dose of 0.5 ${\mu}g$. But intrathecal pretreatment with PTX did not affect pain behavior induced by INF-${\gamma}$. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play important roles in modulating pain behavior induced by pro-inflammatory cytokines administered spinally. Furthermore, TNF-${\alpha}$, IL-1${\beta}$ arid INF-${\gamma}$ administered spinally appear to produce pain behavior by different mechanisms.

• Tuberculosis and Respiratory Diseases
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• 제45권6호
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• pp.1167-1177
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• 1998

연구배경 : 결핵은 우리나라에서 아직도 흔하게 발생하는 질환으로 세포면역반응에 의해 육아종이 형성되며, 이 과정에서 대식세포가 분비하는 tumor necrosis factor-alpha (TNF-$\alpha$), Th1 세포가 생성하는 gamma-Interferon (INF-$\gamma$), 내피 세포가 표현하는 intercelluar adhesion molecule-1 (ICAM-1)이 중요한 역할을 할 것이라고 생각되었다. 방 법 : 저자들은 결핵의 경중(輕重)과 이러한 물질들이 관련이 있는가를 알아보기 위하여, 환자의 혈액을 채취하여 TNF-$\alpha$, INF-$\gamma$를 radioimmuno assay(RIA)로, ICAM-1이 혈액으로 유리된 형태인 sICAM-1을 enzyme linked immunosolvent assay(ELISA)로 각각 측정하였다. 또한 화학 요법에 따른 변화를 알기 위해 치료 시작후 6개월 시점에서 다시 추적검사를 실시하였다. 결 과 : TNF-$\alpha$, INF-$\gamma$, sICAM-1은 중등증과 중증의 결핵에서는 의미 있게 증가하였고, 경증에서는 의의가 없었다. 6개월간의 항결핵 치료후, sICAM-1은 임상경과에 동반하여 의미있는 감소를 보였지만. TNF-$\alpha$, INF-$\gamma$에서는 감소는 있었지만 의의는 없었다. 결 론 : 본 실험 결과 결핵의 세포 면역 매개과정에는 TNF-$\alpha$와 INF-$\gamma$가 매우 중요한 역할을 하며, 그 반응 정도가 질병의 병기에 따라 심할수록 많이 증가함을 관찰하였다. ICAM-1은 TNF-$\alpha$와 INF-$\gamma$ 농도와 비례하여 sICAM-1이 증가하였고, 질병의 병기에 따라 농도의 차이가 있을뿐 아니라, 치료경과에 비례하여 농도변화를 보여, 질병의 할동성을 나타내는 것 외에 치료 경과를 나타내는 지시자로서의 가능이 있을 것으로 생각된다.

• 생명과학회지
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• 제18권11호
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• pp.1471-1478
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• 2008

본 연구에서는 내독소내성 상태에 있는 마우스 세포의 싸이토카인 생성능을 측정하기 위하여 대식세포-림프구 공동배양계를 이용한 nitric oxide (NO) 생성을 조사하였다. 마우스 복강 대식세포에 lipopolysaccharide (LPS)와 interferon-g (IFN-g)를 처리시 NO 생성이 증가되었으며, tumor necrosis factor-a (TNF-a) 또한 LPS처럼 NO 합성을 자극하는 것을 관찰할 수 있었다. 한편, 대식세포를 비장세포와 공동배양시, LPS 단독처리만으로도 NO 합성이 증가되었다. 반면, 2.5 mg/kg LPS로 전처리하고 치사량의 LPS를 2차 투여한 마우스의 경우, 마우스의 치사 및 혈중 TNF-a와 IFN-g가 증가되지 않았다. 또한 LPS-내성 마우스로부터 분리한 대식세포를 정상 비장세포와 공동배양시 LPS에 의한 NO생성이 일어나지 않았으며, 외래 TNF-a에 의한 NO 생성도 일어나지 않았다. 이와 아울러 정상 대식세포와 LPS 내성 마우스로부터 분리한 비장세포를 공동배양하였을 때, LPS 자극으로 인한 NO 생성이 일어나지 않았으며, 이러한 억제현상은 외래 IFN-g 또는 IFN-g 생성을 촉진시키는 concanavalin A (ConA)에 의해서 다시 역전되었다. 이러한 결과는 대식세포 뿐만 아니라 림프구도 LPS 내성에 관여하는 것을 보여준다고 사료된다. INF-g는 TNF-a 발현을 증가시키기 때문에, 림프구의 INF-g 합성 감소는 LPS에 내성을 보이는 대식세포의 TNF-a 합성 저하와 상호작용으로 내독소내성 상태를 유도하며 과도한 염증반응을 억제하는 것으로 사료된다. 따라서 LPS 내독소내성은 중환자의 심각한 패혈증에 대한 예방법으로 활용될 수 있을 것으로 기대된다.

• IMMUNE NETWORK
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• 제3권1호
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• pp.53-60
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• 2003

Background: The role of macrophages in tumor angiogenesis is known to be the production of angiogenic cytokines and growth factors including TNF-${\alpha}$. Recently, macrophage also can produce the INF-${\gamma}$ that is being studied to be involved in angiogenic inhibition. Thus, the importance of macrophages in tumor angiogenesis is might being an angiogenic switch. Thus, the hypothesis tested here is that TNF-${\alpha}$ can modulate the INF-${\gamma}$ production in the macrophages from tumor environment as a part of tumor angiogenic switch. Methods: Macrophages in tumor environment were obtained from the peritoneal cavity of C57BL/6 mice injected with B16F10 melanoma cell line for 6 or 11 days. $Mac1^+$-macrophages were purified using magnetic bead ($MACs^{TM}$; Milteny Biotech, Germany) and cultured with various concentrations of TNF-${\alpha}$ for various time points at $37^{\circ}C$. The supernatants were analyzed for IFN-${\gamma}$ or VEGF by ELISA kit (Endogen, Woburn, MA). Results: Residential macrophages from the peritoneal cavity did not respond to LPS or TNF-${\alpha}$ to produce INF-${\gamma}$. However, the cells from tumor environment produced IFN-${\gamma}$ as well as VEGF and upregulated by the addition of LPS or TNF-${\alpha}$. RT-PCR analysis revealed the external TNF-${\alpha}$-induced IFN-${\gamma}$ gene expression in the macrophages from tumor environment. Conclusion: The overall data suggest that the macrophages in tumor environment might have an important role not only in angiogenic signal but also in anti-angiogenic signal by producing related cytokines. And TNF-${\alpha}$ might be a key cytokine in tumor angiogenic switch.

• Journal of Applied Biological Chemistry
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• 제52권1호
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• pp.21-27
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• 2009

인삼은 가공처리방법에 따라 홍삼과 발효홍삼으로 구분된다. 또한, 이들의 가공처리방법에 따라 인삼의 효능을 나타내는 사포닌의 함량이 차이가 있다. 따라서, 본 연구에서 인삼, 홍삼 및 발효홍삼이 대식세포에서 LPS에 의한 염증에 대한 항염효과 및 그 기전을 규명하고자 하였다. 마우스의 대식세포인 RAW264.7 세포에서 LPS에 의해 유도되는 염증관련인자인 NO 및 COX-2의 발현 및 TNF-$\alpha$, INF-$\gamma$ 그리고 NF-${\kappa}B$의 활성을 인삼, 홍삼 그리고 발효홍삼에 의한 항염효과 차이를 비교 하였다. 그 결과, 인삼 및 홍삼 그리고 발효홍삼 모두에서 LPS에 의한 NO의 생성을 억제시키는 것을 확인하였으며, TNF-$\alpha$ 및 INF-$\gamma$의 생성 또한 억제시키는 것을 알 수 있었다. 또한, 인삼 및 홍삼 그리고 발효홍삼 모두 COX-2의 발현 및 LPS에 의한 $I{\kappa}B$의 인산화를 억제시킴으로써 NF-${\kappa}B$의 활성을 억제시키는 것임을 알 수 있었다. 홍삼이 인삼과 발효홍삼에 비하여 NO의 생성을 더 효과적으로 억제시키는 것은 각각의 제조과정에서 나타나는 인삼사포닌의 조성의 차이에 따른 것으로 추정된다. 본 연구는 단순한 동물세포 수준에서의 비교 차이이며 좀 더 정확한 기전의 규명을 위해서는 향후 동물실험을 통한 비교 실험이 수행되어야 할 것이다.

• 대한수학회지
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• 제36권6호
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• pp.1061-1073
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• 1999

Let X be a real normed linear space. Let T : D(T) ⊂ X \longrightarrow X be a uniformly continuous and ∮-strongly quasi-accretive mapping. Let {${\alpha}$n}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} , {${\beta}$n}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} be two real sequences in [0, 1] satisfying the following conditions: (ⅰ) ${\alpha}$n \longrightarrow0, ${\beta}$n \longrightarrow0, as n \longrightarrow$\infty$ (ⅱ) {{{{ SUM from { { n}=0} to inf }}}} ${\alpha}$=$\infty$. Set Sx=x-Tx for all x $\in$D(T). Assume that {u}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} and {v}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} are two sequences in D(T) satisfying {{{{ SUM from { { n}=0} to inf }}}}∥un∥<$\infty$ and vn\longrightarrow0 as n\longrightarrow$\infty$. Suppose that, for any given x0$\in$X, the Ishikawa type iteration sequence {xn}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} with errors defined by (IS)1 xn+1=(1-${\alpha}$n)xn+${\alpha}$nSyn+un, yn=(1-${\beta}$n)x+${\beta}$nSxn+vn for all n=0, 1, 2 … is well-defined. we prove that {xn}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} converges strongly to the unique zero of T if and only if {Syn}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} is bounded. Several related results deal with iterative approximations of fixed points of ∮-hemicontractions by the ishikawa iteration with errors in a normed linear space. Certain conditions on the iterative parameters {${\alpha}$n}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} , {${\beta}$n}{{{{ { }`_{n=0 } ^{$\infty$ } }}}} and t are also given which guarantee the strong convergence of the iteration processes.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2018년도 춘계학술발표회
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• pp.13-13
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• 2018

The anti-inflammatory (INF) compounds (1-15) were isolated from Agrimonia pilosa Ledeb. (APL) by activity-guided isolation technique. The isolated compounds (1-15) were identified as quercetin-7-O-rhanmoside (1), apigenin-7-O-glycoside (2), kaempferol-7-O-glycoside (3), apigenin-7-O-[6"-(butyl)-glycoside] (4), querceitn (5), kaempferol (6), apigenin (7), apigenin-7-O-[6"-(pentyl)-glycoside] (8), agrimonolide (9), agrimonolide-6-O-glucoside (10), desmethylagrimonolide (11), desmethylagrimonolide-6-O-glucoside (12), luteolin (13), vitexin (14) and isovitexin (15). Flavonoids, compound 2, 3, 11, and 14-15 have been found in APL for the first time. Furthermore, two novel flavone derivatives, compound 4 and 8, have been isolated inceptively in plant. In the no cytotoxicity concentration ranges of $0-20{\mu}M$, nitric oxide (NO) production level of 1-15 was estimated in LPS-treated Raw 264.7 macrophage cells. The flavone aglycones, 7 (apigenin, $IC_{50}=3.69{\pm}0.34{\mu}M$), 13 (luteolin, $IC_{50}=4.62{\pm}0.43{\mu}M$), 6 (kaempferol, $IC_{50}=14.43{\pm}0.23{\mu}M$) and 5 (quercetin, $IC_{50}=19.50{\pm}1.71{\mu}M$), exhibited excellent NO inhibitory (NOI) activity in dose-dependent manner. In the structure activity relationship (SAR) study of apigenin-derivatives (APD), apigenin; Api, apigenin-7-O-glucoside; Api-G, apignenin-7-O-[6"-(butyl)-glycoside]; Api-BG and apignenin-7-O-[6"-(pentyl)-glycoside]; Api-P, from APL on INF activity was investigated. The INF mediators level such as NO, INF-cytokines, NF-KB proteins, iNOS and COX-2 were sharply increased in Raw 264.7 cells by LPS. When pretreatment with APD in INF induced macrophages, NOI activity of Api was most effective than other APD with $IC_{50}$ values of $3.69{\pm}0.77{\mu}M$. And the NOI activity was declined in the following order: Api-BG ($IC_{50}=8.91{\pm}1.18{\mu}M$), Api-PG ($IC_{50}=13.52{\pm}0.85{\mu}M$) and API-G ($IC_{50}=17.30{\pm}0.66{\mu}M$). The NOI activity of two novel compounds, Api-PG and Api-BG were lower than their aglycone; Api, but more effective than Api-G (NOI: Api-PG and Api-BG). And their suppression ability on INF cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA showed the similar tendency. Therefore, the anti-INF mechanism study of Api-PG and Api-BG on nuclear factor-kappa B ($NF-{\kappa}B$) pathway, representative INF mechanism, was investigated and Api was used as positive control. Api-BF was more effectively prevent the than phosphorylation of $pI{\kappa}B$ kinase (p-IKK) and p65 than Api-PG in Raw 264.7 cells. In contrast, Api-PG and Api-BG were not reduced the phosphorylation of inhibitor of kappa B alpha ($I{\kappa}B{\alpha}$). Moreover, pretreatment with Api-PG and Api-BG, dose-dependently inhibited LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNAs and proteins in macrophage cells, and their expression were correlated with their NOI activity. Therefore, APL can be utilized to health promote agent associated with their AIN metabolites.

• Nutritional Sciences
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• 제8권3호
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• pp.153-158
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• 2005

Numerous natural herbal compounds have been reported to inhibit adhesion and migration of leukocytes to the site of inflammation Licorice extracts, which have been widely used in traditional Chinese medicinal preparation, possess various pharmacological effects. Isoliquiritigenin, a biogenetic precursor of flavonoids with various pharmacological effects, is a natural pigment present in licorice. We attempted to explore whether licorice extracts and isoliquiritigenin mitigate monocyte adhesion to tumor necrosis factor-$\alpha$ (TNF-$\alpha$)-activated human umbilical vein endothelial cells (HUVEC). In addition, it was tested whether the inhibition of monocyte adhesion to the activated HUVEC accompanied a reduction in vascular cell adhesion molecule-l expression(VCAM-l). Dry-roasted licorice extracts in methylene chloride but not in ethanol markedly interfered with THP-l monocyte adhesion to INF-$\alpha$-activated endothelial cells. licochalcone A compound isolated from licorice extract in methylene chloride appeared to modestly inhibit the interaction of THP-l monocytes and activated endothelium. In addition, isoliquiritigenin abolished the monocyte adhesion with attenuating VCAM-l protein expression on HUVEC induced by INF-$\alpha$. These results demonstrated that non-polar components from dry-roasted licorice extracts containing licochalcone A as well as isoliquiritigenin were active in blocking monocyte adhesion to cytokine-activated endothelimn, which appeared to be mediated most likely through the inhibition of VCAM-l expression on HUVEC. Therefore, licorice may hamper initial inflammatory events on the vascular endothelium involving induction of endothelial cell adhesion molecules.

• 대한수학회보
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• 제21권2호
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• pp.87-89
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• 1984

Let X be a Banach space, and let B(X) (resp. CB(X), K(X), CV(X)) denote the family of all nonvoid (resp. closed bounded, compact, convex) subsets of X. The Kuratowski measure of noncompactness is defined by the mapping .alpha.$_{k}$: B(X).rarw. $R_{+}$ with .alpha.$_{k}$(A) = inf {r>0 vertical bar A can be covered by a finite number of sets with diameter less than r}.an r}.

• 대한수학회논문집
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• 제10권2호
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• pp.439-442
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• 1995

Let ${X_n : n = 1,2,\cdots}$ be a sequence of pairwise independent identically distributed random vectors taking values in a separable Hilbert space H such that $E \Vert X_1 \Vert = \infty$. Let $S_n = X_1 + X_2 + \cdots + X_n$ and for any real $\alpha$ with $0 < \alpha < 1$ define a sequence ${\gamma_n(\alpha)}$ as $\gamma_n(\alpha) = inf {r : P(\Vert S_n \Vert \leq r) \geq \alpha}$. Then $$ lim_{n \to \infty} sup \Vert S_n \Vert/\gamma_n(\alpha) = \infty $$ holds. This is a generalization of Vvedenskaya[2].