• Clinical and Experimental Pediatrics
• /
• 제52권6호
• /
• pp.680-688
• /
• 2009

목 적 : 류코트리엔은 천식의 병태생리에 중요한 향염증성 매개체이며, 천식이나 운동유발성 천식에서 증가되어 있다. Leukotriene C4 synthase (LTC4S)의 A(-444)C 유전자 다형성과 cysteinyl leukotriene receptor 1 (CysLTR1) T(＋927)C 유전자 다형성이 한국 소아의 천식, 아토피 천식 및 운동유발성 천식과 연관이 있는지 알아보고, 폐기능, 기관지과민성, 총IgE 치에 영향을 미치는지 알아보고자 하였다. 방 법 : 총 856명의 천식 환자와 254명의 천식이 없는 정상아를 대상으로 하여 피부반응검사, 폐기능, 메타콜린 기관지 유발검사, 총 IgE 검사를 실시하였고, 천식 환자를 아토피 천식(699명), 운동유발성 천식(277명)으로 나누어 유전자 다형성과의 연관성을 조사하였다. LTC4S A9-444)C, CysLTR1 T(＋927)C 유전자형은 PCR-restriction fragment length polymorphism 방법으로 분석하였다. 결 과 : LTC4S A(-444)C 및 CysLTR1 T(＋927)C 유전자 다형성은 천식, 아토피 천식, 운동유발성 천식과의 연관성이 없었고, 폐기능, $PC_{20}$, 총IgE에도 차이를 보이지 않았다. 아토피 천식에서 총 호산구수는 변종형 LTC4S 유전자형에서 야생형 보다 높았다. LTC4S A(-444)C와 CysLTR1 T(＋927)C의 유전자-유전자 상호 작용도 천식, 아토피 천식, 운동유발성 천식과의 연관이 없었다. 결 론 : 한국 소아 천식의 표현형, 폐기능, 기관지과민성, 총IgE 농도는 LTC4S A(-444)C와 CysLTR1 T(＋927)C 유전자 다형성, 혹은 유전자-유전자 상호작용과 연관이 없는 것으로 생각된다.

• Restorative Dentistry and Endodontics
• /
• 제21권1호
• /
• pp.353-359
• /
• 1996

The purpose of this study was to investigate the concentrations of Leukotriene B4 in relation to the clinical symptom of pulpitis in human dental pulp. Pulps obtained from 3 groups of teeth: normal uniflamed teeth(N=22), asymptomatic teeth with deep caries or large restorations(N = 21) and symptomatic teeth with the clinical diagnosis of irreversible pulpitis(N = 15). Pulps were dissected from normal un inflamed teeth and extirpated from asymptomatic and symptomatic teeth during routine endodontic treatment and stored in liquid nitrogen ($-70^{\circ}C$). The levels of Leukotriene B4 in individual or pooled pulps were measured by radioimmunoassay and the mean levels of each group were compared statistically(Kruskall-Wallis oneway ANOVA test). The results were as followings : 1. In normal pulp, low levels of Leukotriene B4 were measured. 2. In pulps from asymptomatic and symptomatic teeth had significantly higher levels of Leukotriene B4 than normal pulps(p<0.01). 3. The levels of Leukotriene B4 in pulps from symptomatic teeth were significantly higher than those of pulps from asymptomatic teeth(p<0.01). These results suggest that Leukotriene B4 play a cretain role in inflammatory process of dental pulp and have a relationship with clinical symptoms of pulpitis.

• Clinical and Experimental Pediatrics
• /
• 제48권7호
• /
• pp.766-771
• /
• 2005

목 적 : 류코트리엔 수용체 길항제는 천식의 병리 반응에 관여하는 cysteiny leukotriene의 생성과 작용을 억제하여 급성기 천식 증상의 치료와 천식 증상의 조절 요법에 사용할 수 있다. 본 연구에서는 소아 천식환자에서 cysteinyl leukotriene 생성에 관여하는 $LTC_4S$ 유전자 다형태와 류코트리엔 수용체 길항제인 montelukast의 임상적 효과를 조사하여 약물유전학적 연관성 유무를 알고자 하였다. 방 법 : 환자군은 경증 지속성 천식과 중등증 지속성 천식환자 161명을 대상으로 하였고, montelukast 5 mg을 하루에 한 번씩 총 8주 동안 투여하였다. $LTC_4S$ 유전자 다형태는 restriction fragment length polymorphism을 이용하여 조사하였다. 결 과 : 대조군에서 LTC4S 유전자형의 분포는 A/A, A/C, C/C가 각각 74.0%, 22.6%, 3.4%였고, 환자군에서는 A/A, A/C, C/C가 각각 70.8%, 23.6%, 5.6%였다. 두 군의 유전자형 분포는 통계적으로 유의한 차이를 보이지 않았고, $LTC_4S$ 유전자형 분포와 천식의 중증도 사이에도 유의한 차이가 없었다. 반응군에서는 경증 지속성 천식환자가 반응이 없는 군에서는 중등증 지속성 천식환자가 더 많았다. 전체 소아 천식환자군에서는 montelukast에 대한 반응군과 반응이 없는 군 사이에 $LTC_4S$ 유전자형에 따른 차이는 없었다. 경증 지속성 천식환자의 반응군에서 adenine 대립유전자를 가진 환자가 많았으나, 중등증 지속성 천식환자에서는 유전자형에 따른 반응군과 반응이 없는 군의 유의한 차이가 없었다. 결 론 : 본 연구에서 소아 경증 지속성 천식환자의 경우에는 통계적으로 adenine 대립유전자가 montelukast에 대한 임상적 효과를 예측할 수 있는 인자라고 할 수 있으나 전체 소아 천식환자에서는 $LTC_4S$ 유전자 다형태와 montelukast의 임상적 효과와의 연관성은 통계적으로 없었다.

• Toxicological Research
• /
• 제18권2호
• /
• pp.205-213
• /
• 2002

This study was undertaken to develop a subacute murine model for predicting occurrence of systemic anaphylaxis and to evaluate efficacy of various immunological parameters as the monitoring indices for the occurrence of anaphyalxis. The murine anaphyalxis model was developed through intraperitoneally sensitizing 100 $\mu\textrm{g}$ ovalbumin (OVA) in the presence of 1 mg alum and 300 ng cholera toxin twice a week interval followed by challenging 500 $\mu\textrm{g}$. OVA intravenously. Typical anaphylaxis symptoms were demonstrated at the both BALB/c mice, a strain prone to type-2 response, and C57BL/6 mice. a strain prone to type-1 response. Level of plasma histamine was approximately 50-fold or 30-fold higher in the mice sensitized with OVA than the mice sensitized with alum plus cholera toxin or the saline-treated mice after OVA challenge, respectively. Sensitization and challenge with OVA significantly enhanced plasma leukotriene $B_4$ level but not IgE levels in comparison with the control mice, which indicated the role of leukotriene $B_4$ for progression of anaphyalxis. Furthermore, among mice suffered from anaphylaxis, levels of OVA-specific IgGl were significantly higher in the BALB/c mice than in the C57BL/6 mice, which implied the genetic susceptibility for the induction of systemic anaphylaxis. Conclusively, simultaneous evaluation of histamine, leukotriene $B_4$, and allergen-specific IgG isotype may serve as more efficient monitoring tool for vaccine-related anaphyalxis.

• Archives of Pharmacal Research
• /
• 제22권6호
• /
• pp.549-553
• /
• 1999

The antipruritic effect of DA-5018m a capsaicin derivative, was examined in mice. Male ICR mice were topically pretreated with Zostrix-HP (0.075% capsaicin cream), 0.1%, 0.3% DA-5018 cream or cream base (control) twice daily for 4 days. One hour after the last application, itch was induced either by compound 48/80 ($50{\mu}g$, s.c.) or leukotriene B4 (0.03 nmol, i.d.) injection into the rostral back of the animals, and the number of scratches made by the animals at the injection site was counted for 60 min post-injection. DA-5018 cream (both 0.1 and 0.3%) significantly inhibited compound 48/80-induced scratching when compared with the cream base control (p<0.01), which Zostrix-HP showed minimal inhibition of the scratching behavior. In leukotriene B4-induced itch model, Zostrix-HP and 0.3% DA-5018 cram significantly inhibited the scratching during the first 10-min period (p<0.01). The results suggest that DA-5018 cream can be used as an antipruritic agent and warrant clinical evaluation.

• BMB Reports
• /
• 제41권2호
• /
• pp.139-145
• /
• 2008

We cloned and pharmacologically characterized the guinea pig cysteinyl leukotriene (CysLT) 2 receptor (gpCysLT2). gpCysLT2 consists of 317 amino acids with 75.3%, 75.2%, 73.3% identity to those of humans, mice and rats, respectively. The gpCysLT2 gene is highly expressed in the lung, moderately in eosinophils, skin, spleen, stomach, colon, and modestly in the small intestine. CysLTs accelerated the proliferation of gpCysLT2-expressing HEK293. Leukotriene C4 (LTC4) and Leukotriene D4 (LTD4) enhanced the cell proliferation higher than Bay-u9773, a CysLT2 selective partial agonist and a nonselective antagonist for CysLT receptors. Bay-u9773 did not antagonize the cell proliferation by LTC4 and LTD4. Despite the equipotency of the mitogenic effect among these chemicals, calcium mobilization (CM) levels were variable (LTC4 > LTD4 >> Bay-u9773), and Bay-u9773 antagonized the CM by LTC4. Moreover, the Gi/o inhibitor pertussis toxin perfectly inhibited agonist-induced cell proliferation. These results reveal that cell proliferation via CysLT2 signaling was mediated by Gi/o signaling but independent of calcium mobilization.

• 대한약학회:학술대회논문집
• /
• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
• /
• pp.115.2-115.2
• /
• 2002

• Applied Biological Chemistry
• /
• 제41권4호
• /
• pp.261-264
• /
• 1998

Differently substituted styrylquinoline derivatives (6-9) were synthesized by condensation of quinaldine (1) and corresponding substituted benzaldehydes (2-5). Their relative configuration at C11-C12 and coupling patterns were determined by NMR techniques.

• Biomolecules & Therapeutics
• /
• 제20권6호
• /
• pp.526-531
• /
• 2012

During our on-going studies to identify bioactive compounds in medicinal herbs, we found that saucerneol F (SF), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis), showed in vitro anti-inflammatory activity. In this study, we examined the effects of SF on the generation of 5-lipoxygenase (5-LO) dependent leukotriene $C_4$ ($LTC_4$), cyclooxygenase-2 (COX-2) dependent prostaglandin $D_2$ ($PGD_2$), and on phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated degranulation in SCF-induced mouse bone marrow-derived mast cells (BMMCs). SF inhibited eicosanoid ($PGD_2$ and $LTC_4$) generation and degranulation dose-dependently. To identify the molecular mechanisms underlying the inhibition of eicosanoid generation and degranulation by SF, we examined the effects of SF on the phosphorylation of $PLC{\gamma}1$, intracellular $Ca^{2+}$ influx, the translocation of cytosolic phospholipase $A_2$ ($cPLA_2$) and 5-LO, and on the phosphorylation of MAP kinases (MAPKs). SF was found to reduce intracellular $Ca^{2+}$ influx by inhibiting $PLC{\gamma}1$ phosphorylation and suppressing the nuclear translocations of $cPLA_2$ and 5-LO via the phosphorylations of MAPKs, including extracellular signal-regulated protein kinase-1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Taken together, these results suggest that SF may be useful for regulating mast cell-mediated inflammatory responses by inhibiting degranulation and eicosanoid generation.

• Biomolecules & Therapeutics
• /
• 제23권5호
• /
• pp.421-427
• /
• 2015

Imperatorin has been known to exert many biological functions including anti-inflammatory activity. In this study, we investigated the inhibitory effects of imperatorin on the production of inflammatory mediators in mouse bone marrow-derived mast cells (BMMC). Imperatorin inhibited degranulation and the generation of eicosanoids (leukotriene $C_4$ ($LTC_4$) and prostaglandin $D_2$ ($PGD_2$) in IgE/antigen (Ag)-stimulated BMMC. To elucidate the molecular mechanism involved in this process, we investigated the effect of imperatorin on intracellular signaling in BMMC. Biochemical analyses of the IgE/Ag-mediated signaling pathway demonstrated that imperatorin dramatically attenuated degranulation and the production of 5-lipoxygenase-dependent $LTC_4$ and cyclooxygenase-2-dependent $PGD_2$ through the inhibition of intracellular calcium influx/phospholipase $C{\gamma}1$, cytosolic phospholipase $A_2$/mitogen-activated protein kinases and/or nuclear factor-${\kappa}B$ pathways in BMMC. These results suggest that the effects of imperatorin on inhibition of degranulation and eicosanoid generation through the suppression of multiple steps of IgE/Ag-mediated signaling pathways would be beneficial for the prevention of allergic inflammation.