Leukotrienes (LTs) are known to act as a mediator provoking tissue response in inflammation. LTs, particularly type B4 (LTB4) as chemotactic factor of neutrophil are released from neutrophils and gastric mucosal cells when these cells are stimulated by Helicobacter pylori. The present study was performed to test a possibility that eupatilin may prevent the H. pylori-induced gastric cell damage by observing whether this chemical inhibit the release of LTB4 from H. pylori-stimulated gastric cells (Kato III) and neutrophils. As observed in the previous study, H. pylori induced the release of LTB4 from these cells and at the same influx of Ca2+ into the cells. In the presence of eupatilin, the release of LTB4 was inhibited whereas Ca2+ influx was not affected. Probably eupatilin may inhibit the release of LTB4 by preventing the synthesis of LTs. These results suggest that eupatilin can has a therapeutic effect on H. pylori-induced gasric cell damage.
Helicobacter pylori* ; Helicobacter* ; Inflammation ; Leukotriene B4* ; Leukotrienes ; Neutrophils*

Cysteinyl leukotrienes (cys-LTs) are potent mediators of inflammation derived from arachidonic acid through the 5-lipoxygenase/leukotriene C4 synthase pathway. The derivation of their chemical structures and identification of their pharmacologic properties predated the cloning of their classical receptors and the development of drugs that modify their synthesis and actions. Recent studies have revealed unanticipated insights into the regulation of cys-LT synthesis, the function of the cys-LTs in innate and adaptive immunity and human disease, and the identification of a new receptor for the cys-LTs. This review highlights these studies and summarizes their potential pathobiologic and therapeutic implications.
Adaptive Immunity ; Arachidonate 5-Lipoxygenase ; Arachidonic Acid ; Asthma ; Clone Cells ; Cloning, Organism ; Humans ; Inflammation Mediators ; Leukotrienes*

It has been implicated that leukotrienes play roles in the pathogenesis of gastritis and gastric ulceration associated with Helicobacter pylori (H. pylori). Rebamipide is being used as an antiulcer drug but it's mechanism of action has not been understood well. One possible mechanism of action of this drug is to inhibit the cellular release of leukotrienes by various stimuli, particularly H. pylori. In the present study, attempts were made to test this possibility and the results are as follows. When Kato III cells (gastric adenoma cells) were stimulated by H. pylori, leukotriene D4 (LTD4) was released and rebamipide inhibited this release dose-dependently. Similar experiment was performed on neutrophils because the infilteration of neutrophils is a common phenomenon in H. pylori-infected gasrtric tissues. Neutrophils released LTD4 when these cells were stimulated by H. pylori and rebamipide also inhibited this release. Furthermore, rebamipide inhibited the release of LTD from neutrophils induced by calcium ionophore A23187 and arachidonic acid. The results suggest that rebamipide has the action to inhibit the release of LTD4 from various cells and this action may contribute in part to prevent the ulcerogenesis induced by H. pylori.
Adenoma ; Arachidonic Acid ; Calcimycin ; Calcium ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Leukotriene D4* ; Leukotrienes ; Neutrophils ; Stomach Ulcer

Chronic spontaneous urticaria (CSU) is characterized by typically short-lived and fleeting wheals, angioedema or both, which occur spontaneously and persist for longer than 6 weeks. This term is applied to the most common subtype of chronic urticaria. The underlying pathophysiology for CSU involves mast cell and basophil degranulation with release of histamine, leukotrienes, prostaglandins and other inflammatory mediators. Although a variety of treatments exist, many patients do not tolerate or benefit from the existing therapies and even require more effective treatments. Omalizumab is currently the only licensed biologic for antihistamine-refractory CSU, and novel drugs are under development. This article reviews its current status regarding pathogenesis and approach to treatment as well as therapeutic agents that are under development for the treatment of CSU.
Angioedema ; Basophils ; Biological Products ; Histamine ; Humans ; Leukotrienes ; Mast Cells ; Omalizumab ; Prostaglandins ; Urticaria

Lipoxygenase is a protein with non-heme iron atom, which has been discovered in many animals and plants. Lipoxygenase which has a close relationship with human tumors, inflammatory diseases, asthma, arteriosclerosis, and toxic action of chemicals could not only di-oxygenate endogenous polyunsaturated fatty acid to yield bioactive factors such as leukotrienes(LTs), but also has co-oxidation activity to activate xenobiotics. Lipoxygenase inhibitors include hydroxamic acid derivatives, nordihydroguaiaretic acid, flavonoids, FLAP inhibitors and so on. All of them can effectively restrain the catalytic action of lipoxygenase. Literatures demonstrate that the inhibitors can block the formation of relevant bioactive factors and toxic products of xenobiotics clinically which are used to prevent and cure the relevant diseases to keep people healthy.
Animals ; Flavonoids ; pharmacology ; Humans ; Leukotrienes ; metabolism ; Lipoxygenase Inhibitors ; pharmacology ; Masoprocol ; pharmacology ; Oxidation-Reduction ; Xenobiotics ; metabolism

Leukotrienes (LTs) are known to act as a mediator provoking tissue response in inflammation. This finding implicates that LTs also play important roles in the pathogenesis of H. pylori-induced gastritis and gastric ulceration. Rebamipide is being currently used as a therapeutics for gastritis and peptic ulcer, but their mechanisms of action have not been known clearly yet. One possibility is that their therapeutic effects are ascribed to interfering with the H. pylori-induced release of LTs from neutrophils and gastric mucosal cells. In the present study, this possibility was tested using LTB4 as the test material in human neutrophils and Kato III cells(gastric adenoma cells as a substitute for gastric mucosal cells). The release of LTB4 from both neutrophils and Kato III cells was time and H. pylori-dose dependent. The maximum release of LTB4 was induced by neutrophils and Kato III cells when these cells incubated with H. pylori 4.8 X 108 cells/ml for 30 min. But in the presence of rebamipide the release of LTB4 from these cells was suppressed in dose dependent manners. The release was completely suppressed at 1.0 mM of rebamipide in neutrophils and 2.0 mM of this drug in Kato III cells, respectively. We also obtained the results that the release of LTB4 was induced by A23187 (Ca2+ ionophore) and the A23187-induced release was also inhibited by rebamipide. It seems that the mechanism of action of rebamipide is through its interaction with the level of intracellular Ca2+. In view of the roles of LTB4 in inflammatory reaction and the roles of H. pylori in gastritis and peptic ulcer, the effects of this drug observed in this study may contribute to their therapeutic action in these gastric disorders.
Adenoma ; Calcimycin ; Gastritis ; Helicobacter pylori* ; Helicobacter* ; Humans ; Inflammation ; Leukotriene B4* ; Leukotrienes ; Neutrophils ; Peptic Ulcer ; Stomach Ulcer

With the acceleration of aging society, delaying aging or promoting healthy aging has become a major demand for human health. 5-Lipoxygenase (5-LOX) is a key enzyme catalyzing arachidonic acid into leukotrienes (LTs), which is a potent mediator of the inflammatory response. Previous studies showed that abnormal activation of 5-LOX and overproduction of LTs are closely related to the occurrence and development of aging-related inflammatory diseases. Therefore, inhibiting 5-LOX activation is a possibly potential strategy for treating age-related diseases. In this paper, the latest research progress in 5-LOX activation, 5-LOX in mediating aging-related diseases and its small molecule inhibitors is briefly reviewed to provide scientific theoretical basis and new ideas for the prevention and treatment of aging-related inflammatory diseases.
Humans ; Arachidonate 5-Lipoxygenase ; Leukotrienes ; Arachidonic Acid ; Aging ; Lipoxygenase Inhibitors/pharmacology*

BACKGROUND: Exercise can aggravate asthmatic symptoms in many patients with bronchial asthma. It is caused by that inhaled air bypasses nasal cavity and goes directly to the lower airways through open mouth dring exercise. Although the pathogenetic mechanisms of exercise-induced asthma(EIA) have not been clarified yet, there is evidence that chemical mediators, released from the inflammatory cells triggered by airway cooling or drying, might be responsible for induction of bronchoconstriction. However, it has been controversial which chemical mediators or cells are involved in such process. Objectiye . The aim of this study was to evaluate the role of activated mast cells in the pathogenesis of EIA and find out whether or not sulfidopeptide leukotrienes (LTC4/d4/E4) are involved in the exercise-induced bronchoconstriction. MATERIAL AND METHOD: Eleven asthmatics with documented exercise-induced bronchoconstriction and 10 control subjects were studied. Before and 6 hours after free running for 6 minutes, forced expiratory volume in 1 second (FEV,) and the concentrations of N- methylhistamine, LTE4, and creatinine in unine collected for 6 hours after exercise were determined. RESULT: Urinary concentrations of N-methylhistamine(mean+SE, ng/mg creatinine) of EIA patients before and after exercise were 159+40 and 450+75, respectively. Those of control subjects were 208+ 54 and 275+ 62, respectively. Uninary N-methylhistamine levels of EIA group increased significantly after exercise, while those of control group did not change. Urinary concentrations of LTE,(mean+SE, pg/mg creatinine) of EIA patients before and after exercise were 15.6 k2.6 and 22.2+5.8, respectively. Those of control subjects were 10.4+ 4.0, 18.2 +7.0, respectively. The concentrations of LTE4 in the urine samples collected before exerise revealed no difference between EIA and control subjects (p=0.07). There was no change after exercise in both groups. Percent fall of FEV, was 29.1+8.0% (mean+SD) in EIA group and 3.4 + 4.0% in control group, respectively. There was no correlation between reduction of FEV, and change in urinary concentrations of N-methyl-histmine after exercise. CONCLUSTION: Chemical mediators of activated mast cells may be involved in exercise-induced bronchoconstriction, but there is little evidence for enhanced sulfidopeptide leukotriene generation as assessed by urinary LTE4.
Asthma ; Asthma, Exercise-Induced* ; Bronchoconstriction ; Creatinine ; Forced Expiratory Volume ; Humans ; Leukotriene E4 ; Leukotrienes ; Mast Cells ; Mouth ; Nasal Cavity ; Running

BACKGROUND: Theophylline has been used in the treatment of asthma for decades as a broncho- dilator, but recent studies suggested that it has anti-inflammatory and immunomodulatory properties. OBJECTIVE: The aim of this study was to determine the effect of theophylline therapy on urinary excretion of leukotriene B4 (LTB4) and C4 (LTC4), which have been known to play a role in the airway inflammation in asthmatic patients. METHODS: Fifty-one patients, aged 13 months to 6 years, who were hospitalized with asthma were randomized in to 3 groups according to treatment regimen. Twenty-one patients were administered theophylline with budesonide and salbutamol inhalation (Group 1). Fifteen patients were treated with budesonide and salbutamol inhalation (Group 2) and the other fifteen patients with salbutamol inhalation only (Group 3). Urine samples for the determination of LTB4 and LTC4 were collected on admission and on the fifth hospital day in each patient. The concentrations of urinary leukotrienes were measured by ELISA (Neogen, U.S.A.) and corrected by urinary creatinine levels. Ten controls were also studied. RESULTS: The initial urinary LTC4 levels in asthmatic children were significantly higher than in controls. Urinary LTC4 was significantly decreased after treatment compared with the initial level in group 1 (p<0.05), but not in groups 2 and 3. Urinary LTB4 did not show significant difference between patients and controls on admission and showed no significant change after treatment compared with the initial levels in all three groups. CONCLUSION: These results suggest that the suppression of LTC4 synthesis is one of the anti-inflammatory mechanisms of theophylline and support the use of theophylline as a the rapeutic agent in asthmatic patients.
Albuterol ; Asthma* ; Budesonide ; Child* ; Creatinine ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; Inhalation ; Leukotriene B4* ; Leukotriene C4 ; Leukotrienes ; Theophylline*

Lipid mediators contribute to inflammation providing both pro-inflammatory signals and terminating the inflammatory process by activation of macrophages. Among the most significant biologically lipid mediators, these are produced by free-radical or enzymatic oxygenation of arachidonic acid named "eicosanoids". There were some novel eicosanoids identified within the last decade, and many of them are measurable in clinical samples by affordable chromatography-mass spectrometry equipment or sensitive immunoassays. In this review, we present some recent advances in understanding of the signaling by eicosanoid mediators during asthmatic airway inflammation. Eicosanoid profiling in the exhaled breath condensate, induced sputum, or their metabolites measurements in urine is complementary to the cellular phenotyping of asthmatic inflammation. Special attention is paid to aspirin-exacerbated respiratory disease, a phenotype of asthma manifested by the most profound changes in the profile of eicosanoids produced. A hallmark of this type of asthma with hypersensitivity to non-steroid anti-inflammatory drugs (NSAIDs) is to increase biosynthesis of cysteinyl leukotrienes on the systemic level. It depends on transcellular biosynthesis of leukotriene C₄ by platelets that adhere to granulocytes releasing leukotriene A₄. However, other abnormalities are also reported in this type of asthma as a resistance to anti-inflammatory activity of prostaglandin E₂ or a robust eosinophil interferon-γ response resulting in cysteinyl leukotrienes production. A novel mechanism is also discussed in which an isoprostane structurally related to prostaglandin E₂ is released into exhaled breath condensate during a provoked asthmatic attack. However, it is concluded that any single eicosanoid or even their complex profile can hardly provide a thorough explanation for the mechanism of asthmatic inflammation.
Arachidonic Acid ; Asthma ; Eicosanoids ; Eosinophils ; Granulocytes ; Humans ; Hypersensitivity ; Immunoassay ; Inflammation* ; Isoprostanes ; Leukotrienes ; Macrophages ; Oxygen ; Phenotype ; Spectrum Analysis ; Sputum