• Title/Summary/Keyword: Leukotriene

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Biology of melanocytes and melanogenesis (멜라닌세포의 특성과 멜라닌 형성)

  • 박경찬
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.25 no.2
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    • pp.45-57
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    • 1999
  • Melanocytes, derived from neural crest, make melanin and protect skin from the hazardous ultraviolet light. Melanocytes with dendritic process has similar morphology with neurogenic cells and share growth factor receptors such as neurotrophin receptors. Melanogenesis can be regulated by ultraviolet light and inflammation of the skin. In addition, several factors such as hormone, cytokines, arachidonic acid can affect the proliferation and melanogenesis of melanocytes. For melanogenesis, melanocytes need expression of various genes including tyrosinase, TRP-1, TRP-2. In addition, melanin need to be transferred from melanocytes to surrounding keratinocytes. The biology of melanocytes is complex and mechanism of melanocytes proliferation and melanogenesis is still under the investigation.

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Inhibitory Effect of Panax notoginseng on Nitric Oxide Synthase, Cyclo-oxygenase-2 and Neutrophil Functions

  • Park, Soon-Gi;Joo, Shin-Tak;Ban, Chang-Gyu;Moon, Jin-Young;Park, Sun-Dong;Park, Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.5
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    • pp.1295-1302
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    • 2006
  • Our preliminary aim is to elucidate the pharmacokinetic features of the PNS(Panax notoginseng Buck F.H. Chen. (Arialiaceae) root). First, we assessed the prevention of neurtrophil functions. A Panax notoginseng inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. This Panax notoginseng reduced nitric oxide (NO) and prostaglandin E2 production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. Panax notoginseng significantly reduced mouse paw oedema induced by carrageenan. The results indicate that Panax notoginseng exerts anti-inflammatory effects related to the inhibition of neutrophil functions and of NO and prostaglandin E2 production, which could be due to a decreased expression of inducible NO synthase and cyclo-oxygenase-2.

Anti-allergic and Anti-inflammatory Actions of Cimicifuga heracleifolia: Partial Purification of Active Components

  • Kim, Young-Ran;Park, Soo-Hyung;Kim, Kyeong-Man
    • Biomolecules & Therapeutics
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    • v.2 no.2
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    • pp.149-154
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    • 1994
  • Anti-allergic and anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were evaluated in mice and rats. Several criteria were employed to assess the anti-allergic and anti-inflammatory actions of Cimicifuga heracleifolia, such as hyaluronidase activity, mediators-induced vascular permeability changes, 48 hour homologous passive cutaneous anaphylaxis (PCA) histamine release from mast cells, and the carrageenan-induced rat paw edema. To further characterize the active components, the water extract was either extracted with organic solvent or fractionated according to molecular weight, and each fraction was tested for some of anti-allergic parameters. Hyaluronidase activities, both in activating and in activated states, were significantly inhibited by the water extract of Cimicifuga heracleifolia and by some of its subfractions, molecular weight less than 1,000. The water extracts (50~400 mg/kg) significantly inhibited 48 hr homologous PCA and vascular permeability changes induced by chemical mediators (histamine, serotonin, and leukotriene $C_4$) in mice. In the case of histamine-induced vascular permeability changes, more extensive studies were conducted; water extract was either fractionated according to molecular weight or extracted with butanol. Anti-histamine actions were observed only from the water layer, and these active components were of the molecular weight less than 1,000. These anti-allergic actions were observed mainly from mice than from rats. On the other hand, anti-inflammatory actions of the water extract from Cimicifuga heracleifolia were significant in rats.

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Effects of Pranlukast on Ovalbumin Induced Early-Phase Bronchoconstriction in Guinea Pigs (기니픽에서 Ovalbumin으로 유발된 즉시형 기관지 수축반응에 대한 Pranlukast의 효과)

  • Lee, Sin-Hyung;Shim, Jae-Jeong;Kim, Kyung-Kyu;Jeong, Hye-Cheol;Kwon, Young-Hwan;Kim, Je-Hyeong;Lee, Sung-Yong;Lee, So-Ra;Lee, Sang-Youb;Cho, Jae-Youn;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.697-708
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    • 1999
  • Background : Leukotriene (LT) $C_4$, $D_4$, and $E_4$, the main components of slow-reacting substance of anaphylaxis (SRS-A), have been suggested to play an important role in bronchial asthma such as antigen-induced bronchoconstriction, airway hyperreactivity, and pulmonary eosinophil accumulation. The purpose of this study was to evaluate the effects of treatment with the cysteinyl-LTs (cys-LTs) antagonist, pranlukast on allergen-induced guinea pig asthma model. Methods : Guinea pigs of treatment and placebo groups were sensitized by subcutaneous injection of ovalbumin(OVA) and challenged by inhalation of aerosolized OVA (1% weight/volume OVA). Normal control group did not sensitize with OVA. Oral ingestion of pranlukast and normal saline to the treatment and placebo groups was performed. In the treatment and placebo groups, airway resistance was measured before and after oral ingestion. Serum $LTC_4$ and eosinophilic infiltration of the bronchiolar and peribronchiolar tissues were measured after ingestion in the treatment and placebo groups. Results : Allergen-induced airway constriction developed in 20 (8 in treatment group, 12 in placebo group) among 35 guinea pigs. Airway resistance was significantly decreased at 3 and 6 minutes after OVA challenge in the pranlukast treatment group. In the placebo group, there was no difference of airway resistance between before and after saline ingestion. Serum $LTC_4$ levels showed 348.4 pg/ml in the treatment group, 373.9 pg/ml in the placebo group, and 364.4 pg/ml in the control group. There were no statistically significant difference between treatment and placebo group (p=0.232), and treatment and control group (p=0.501). Eosinophilic infiltrations in the peribronchiolar region per one-microscopic field ($\times$400 high power fields) demonstrated 7.06 in the treatment group, 19.2 in the placebo group, and 4.50 in the control group. There was significant decrement of eosinophilic infiltration in the treatment group which was compared with placebo group (p=0.001). Conclusion : These results demonstrate that pranlukast, a cys-LTs receptor antagonist, can attenuate allergen induced early-phase bronchoconstriction and eosinophilic infiltration in the bronchiolar tissues.

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Cromakalim Blocks Membrane Phosphoinositide Activated Signals in the Guinea Pig Lung Mast Cells Stimulated with Antigen-Antibody Reactions

  • Ro, Jai-Youl;Kim, Ji-Young;Kim, Kyung-Hwan
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.2
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    • pp.251-260
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    • 1998
  • Cromakalim (BRL 34915), known as an airway smooth muscle relaxant, inhibited the releases of mediators in the antigen-induced mast cell activation. It has been suggested that cromakalim, in part, inhibited mediator releases by inhibiting the initial increase of 1,2-diacylglycerol (DAG) produced by the activation of the other phospholipase system which is different from phosphatidylcholine-phospholipase D pathway. The aim of this study is to further examine the inhibitory mechanism of cromakalim on the mediator release in the mast cell activation. Guinea pig lung mast cells were purified by using enzyme digestion and percoll density gradient. In purified mast cells prelabeled with $[^3H]PIP_2$, phospholipase C (PLC) activity was assessed by the production of $[^3H]$insitol phosphates. Protein kinase C (PKC) activity was assessed by measuring the protein phosphorylated from mast cells prelabeled with $[{\gamma}-32P]ATP$, and Phospholipase $A_2\;(PLA_2)$ activity by measuring the lyso-phosphatidylcholine produced from mast cell prelabeled with 1-palmitoyl-2-arachidonyl $phosphatidyl-[^{14}C]choline$. Histamine was assayed by fluorometric analyzer, and leukotrienes by radioimmunoassay. The PLC activity was increased by activation of the passively sensitized mast cells. This increased PLC activity was decreased by cromakalim pretreatment. The PKC activity increased by the activation of the passively sensitized mast cells was decreased by calphostin C, staurosporine and cromakalim, respectively. The $PLA_2$ activity was increased in the activated mast cells. The pretreatment of cromakalim did not significantly decrease $PLA_2$ activity. These data show that cromakalim inhibits histamine release by continuously inhibiting signal transduction processes which is mediated via PLC pathway during mast cell activation, but that cromakalim does not affect $PLA_2$ activity related to leukotriene release.

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New evidence on mechanisms of action of spa therapy in rheumatic diseases

  • Tenti, Sara;Fioravanti, Antonella;Guidelli, Giacomo Maria;Pascarelli, Nicola Antonio;Cheleschi, Sara
    • CELLMED
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    • v.4 no.1
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    • pp.3.1-3.8
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    • 2014
  • Spa represents a treatment widely used in many rheumatic diseases (RD). The mechanisms by which immersion in mineral or thermal water ameliorates RD are not fully understood. The net benefit is probably the result of a combination of factors, among which the mechanical, thermal and chemical effects are most prominent. Buoyancy, immersion, resistance and temperature play important roles. According to the gate theory, pain relief may be due to the pressure and temperature of the water on skin; heat may reduce muscle spasm and increase the pain threshold. Mud-bath therapy increases plasma ${\beta}$-endorphin levels and secretion of corticotrophin, cortisol, growth hormone and prolactin. It has recently been demonstrated that thermal mud-bath therapy induces a reduction in circulating levels of prostaglandin E2, leukotriene B4, interleukin-$1{\beta}$ and tumour necrosis factor-${\alpha}$, important mediators of inflammation and pain. Furthermore, balneotherapy has been found to cause an increase in insulin-like growth factor-1, which stimulates cartilage metabolism, and transforming growth factor-${\beta}$. Beneficial anti-inflammatory and anti-degenerative effects of mineral water were confirmed in chondrocytes cultures, too. Various studies in vitro and in humans have highlighted the positive action of mud-packs and thermal baths, especially sulphurous ones, on the oxidant/antioxidant system. Overall, thermal stress has an immunosuppressive effect. Many other non-specific factors may also contribute to the beneficial effects observed after spa therapy in some RD, including effects on cardiovascular risk factors (e.g. adipokines) and changes in the environment, pleasant surroundings and the absence of work duties.

Study on Anti-thrombotic Activity, Superoxide Generation in Human Neutrophils and Platelet Aggregation in Human Blood of Hwao-tang

  • Park Won Hwan;Park Soo Young;Park Tae Woo;Kim Jong Gu;Kim Seog Ha;Kim Cherl Ho
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.5
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    • pp.1494-1504
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    • 2004
  • The present paper reports the effects of Hwaotang an atherosclerosis using a spontaneous experimental model, We have also investigated the pharmacological effect of Hwaotang on collagen- and ADP-induced blood platelet aggregation, thrombin-induced conversion of fibrinogen and fibrinolysis in in vitro experiments, and various effects on stimuli-induced superoxide generation in human neutrophils. Hwao-tang was shown to have inhibitory effect on collagen- and ADP-induced blood platelet aggregation, on thrombin-induced conversion of fibrinogen to fibrin and on the activity of plasminogen or plasmin. Hwao-tang also significantly inhibited fMLP-induced superoxide generation in a concentration-dependent manner, but not that induced by arachidonic acid. Hwao-tang inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B4 production, without any effect on 5-lipoxygenase activity. In conclusion, the protection of extracts of Hwao-tang on the ischemic infarction induced artificially might be involved to their inhibition of thrombotic action. The results also indicate that Hwao-tang exerts the effects on superoxide generation related to the inhibition of neutrophil functions.

Effect of Cheongawongagam Extract on the Ovariectomized Rat Model of Osteoporosis (청아원가감 추출물이 난소적출로 유발된 흰쥐의 골다공증 모델이 미치는 영향)

  • Yun, Gee Won;Lee, Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.34 no.1
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    • pp.14-23
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    • 2020
  • This study was conducted to evaluate the efficacy of Cheongawongagam on osteoporosis rat. A total of 35 rats were divided into seven groups; Normal control(SD-Nr), experimental control group(OVX-CTL), positive control group(OVX-17β-E2) and herb extracts group[Eucommia ulmoides(OVX-EU-E), Juglandis semen(OVX-JR-SE), Acanthopanax senticosus(OVX-AS-E) extract and Cheongawongagam extracts(OVX-JAEG-E)]. All control group, and herb extracts group were ovariectomized. After the 3 weeks recovery period, herb extract group were orally administered 200 mg / kg of the EU-E, JR-SE, AS-E and JAEG-E for 12 weeks. In the OVX-CTL, 17β-estradiol(E2) was administered subcutaneously on the back of the rats at a dose of 0.03 ug/sc. Their body weight, serum total cholesterol, triglyceride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Leukotriene B4 (LTB4), calcium (Ca), estradiol, osteocalcin, and deoxypyridinoline (DPD) concentration were measured. Also, we investigated mRNA expression of inflammatory cytokine, MMP-2, MMP-9, and bone tissue. As a result, total cholesterol was significantly decreased in the OVX-AS-E and OVX-JAEG-E. ALP was significantly increased and osteocalcin, DPD was significantly decreased in OVX-JAEG-E. The expression of inflammatory mediators (TNF-α, IL-1β, LTB4, COX-2, NOS-2), inflammatory cytokines IL-1β and MMP-9 mRNA were significantly decreased in OVX-JAEG-E. Histologic examination of the femur showed that bone mineral density, and bone mass were increased and bone marrow were decreased in the OVX-JAEG-E group. The above experiment shows that cheongawongagam extract were effective in the prevention and treatment of osteoporosis.

ANALYSIS OF TMJ STATUS IN THE PATIENTS WITH MANDIBULAR FRACTURES: PRELIMINARY STUDY ARTHROSCOPIC EXAMINATION, HISTOMORPHOLOGY AND JOINT FLUID ANALYSIS (하악골 골절 환자들의 악관절 상태 평가: 일차보고 관절내시경적 검사, 조직형태학적 및 관절활액 분석)

  • Kim, Young-Kyun;Kim, Hyoun-Tae;Lee, Do-Hoon;Choi, Yoon-Jung;Chung, Hoon
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.27 no.4
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    • pp.308-313
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    • 2001
  • The purpose of this study is to validate the potential etiologic factors for temporomandibular disorder(TMD). TMJ arthroscopic examination was performed in upper joint compartment of 32 joints from 20 patients with mandibular fractures. Synovial fluid was collected from the upper joint space during pumping manipulation with normal saline. Cytologic smearing and histomorphologic exam of synovial fluid were performed in 15 joints. Prostaglandin $E_2(PGE_2)$ concentration was measured in 11 joints. Leukotriene $B_4(LTB_4)$ concentration was measured in 8 joints. There were several arthroscopic variables such as ecchymosis, fibrillation, and adhesion. Histomorphologic exam showed a variety of findings such as bloody smears, cellular cluster, degenerated cells and cartilage, undifferentiated crystal. Mean $PGE_2$ concentrations were 316.5 pg/ml. Mean LTB4 concentrations were 45.9pg/ml. This study demonstrated a variety of findings on inflammatory and degenerative changes of TMJ. Because acute trauma such as mandibular fracture is a major etiologic factor in cartilage degradation and biochemical and intraarticular pathology, clinicians must identify and address TMJ signs and symptoms during follow-up periods in the long term.

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Detection and Characterization of Two Novel Forms of A Cytosolic Phospholipase $A_2$-Activating Factor in Bovine Brain

  • Park, Jae-Sin;Jung, Kwang-Mook;Jung, Sung-Yun;Na, Doe-Sun;Kim, Dae-Kyong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.187-187
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    • 1996
  • 세포질에 존재하는 100 kDa Phospholipase $A_2$(cPLA$_2$)는 인지질의 sn-2 위치의 에스테르결합을 가수분해함으로서 Prostaglandin과 Leukotriene등 Eicosanoids 생합성의 전구체인 아라키돈산과 Platelet activating factor(PAF)를 생합성하는 전구체를 동시에 생성시키는 효소로 염증과 세포손상등에 중요한 역할이 기대된다. 본 효소의 활성화 기전을 규명하고자 하는 최근의 활발한 연구에도 불구하고 불명확한 점이 많은 것이 현실이다. 특히 세포를 자극하였을 때 유리되는 아라키돈산의 증가율과 세포를 파괴한 후 조제한 가용성분획에서 측정한 활성의 증가율과는 많은 차이를 나타냈다. 이러한 결과부터 cPLA$_2$ 효소 자체를 활성화시키는 어떤 인자를 가정하였다. 최근, PLA$_2$의 또다른 형태인 14 kDa의 분비성 PLA$_2$의 in vitro 활성을 증가시키는 인자가 동정되어 그 생화학적 특성이 규명되고 있으나 이 인자는 cPLA$_2$의 활성에는 아무런 증가효과를 나타내지 않았다. 본 연구자들은 소의 뇌조직에서 cPLA$_2$의 활성을 증가시키는 인자를 발견하고 그의 생화학적인 특성을 규명하였다. 돼지 비장에서 정제한 cPLA$_2$를 사용하였으며 소의 뇌 조직의 가용성 분획으로부터 본 활성화 인자를 동정하였으며 그 활성분획을 양이온 크로마토그라피로서 Mono S EPLC와 Superose 12 Sepharose gel filtration 크로마토그라피를 이용하여 더욱 분리한 결과 약 70 kDa과 25 kDa에서 각각 용출되었다. 이렇게 부분정제한 활성은 췌장에서 분리한 group I과 흰주의 group I과 흰주의 혈소판에서 분리한 group II PLA$_2$에 대해서는 아무런 증가효과를 나타내지 않는 반면, cPLA$_2$의 활성만을 약 5배 증가시켰다. 본 활성은 cPLA$_2$ 효소량의 증가에 따라 활성의 증가효과가 정차 감소하므로 화학량적인 반응(Stoichiometric reaction)일 것으로 예상되었다.

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