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

OBJECTIVETo investigate the role of leukotrienes (LTs) in the progress of children's Henoch-Schoenlein purpura (HSP) nephritis (HSPN), and to provide an experimental basis for clinical application of leukotrienes antagonists in treatment of HSPN.

METHODSThe serum and urine samples were collected from 34 patients with HSPN 18 of them received renal biopsy, 27 cases with HSP and 16 healthy children as control. The level of LTB4 in the serum and urine was tested by enzyme-linked immunosorbent assay (ELISA) and LTE4 in urine in each group by enzyme immunoassay (EIA). The extent of expression of LTC4 synthase was detected by indirect immune fluorescence (IIF) in the renal tissue of 18 HSPN cases who received renal needle biopsy. Meanwhile, 3 cases with thin basement membrane nephropathy (TBMN) and 4 cases with simple hematuria were enrolled as controls. The results of pathological examination of the 4 cases with simple hematuria was normal by light microscope or electron microscope. At the same time, total urine protein in 24 hours was determined in 24 HSPN patients.

RESULT(1) The level of serum and urinary LTB4 in the children with HSPN was (1164.33 +/- 300.28) ng/L and (841.19 +/- 115.23) ng/L, respectively. The level of serum and urinary LTB4 in those with HSP was (559.60 +/- 180.23) ng/L and (574.42 +/- 101.17) ng/L, respectively. The level of serum and urinary LTB4 in the control group was (211.95 +/- 67.72) ng/L and (227.33 +/- 76.12) ng/L, respectively. There was significant difference in the LTB4 level between HSPN group and HSP group (P < 0.01) while there was statistically significant difference in the LTB4 level between HSPN group and control group (P < 0.01). The urinary LTE4 was (1252.31 +/- 251.62) ng/L, (805.93 +/- 185.52) ng/L and (149.51 +/- 33.66) ng/L for HSPN group, HSP group and control group, respectively, and the differences were significant (P < 0.01). (2) The increase of serum and urinary LTB4 and urinary LTE4 was closely relative to the severity of histopathological changes. (3) Serum and urinary LTB4, urinary LTE4 increased in parallel to the enhancement of urine protein in HSPN patients (P < 0.01 or P < 0.05). (4) Markedly significant difference of LTC4 synthase by IIF existed between HSPN groups and control group.

CONCLUSIONLTs can promote the progress of children's HSPN. There is a close relationship between LTs expression in renal tissues, the pathological severity of HSPN and proteinuria.

Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Leukotrienes ; metabolism ; Male ; Nephritis ; etiology ; metabolism ; Proteinuria ; metabolism ; Purpura, Schoenlein-Henoch ; complications ; metabolism

Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; however, the exact mechanisms of such chronic eosinophilic inflammation are not fully understood. Cysteinyl leukotriene over-production may be a key factor in the induction of eosinophilic activation. Genetic studies have suggested a role for variability of genes in disease susceptibility and response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1* 301, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10 -1082A > G, ACE -262A > T, and CRTH2 -466T > C; the four-locus SNP set was composed of B2ADR 46A > G, CCR3 -520T > G, CysLTR1 -634C > T, and FCER1B -109T > C. Management of AERD is an important issue. Aspirin ingestion may result in significant morbidity and mortality, and patients must be advised regarding aspirin risk. Leukotriene receptor antagonists (LTRA) that inhibit leukotriene pathways have an established role in long-term AERD management and rhinosinusitis. Aspirin desensitization may be required for the relief of upper and lower airway symptoms in AERD patients. Future research should focus on identification of biomarkers for a comprehensive diagnostic approach.
Animals ; Asthma, Aspirin-Induced/drug therapy/*genetics/*immunology ; Eosinophils/metabolism ; Genetic Predisposition to Disease/genetics ; Humans ; Leukotriene Antagonists/therapeutic use ; Leukotrienes/metabolism ; Models, Biological ; Polymorphism, Genetic/genetics/physiology

Animals ; Asthma ; drug therapy ; immunology ; metabolism ; physiopathology ; Child, Preschool ; Humans ; Infant ; Leukotrienes ; immunology ; metabolism ; pharmacology ; Respiratory Sounds ; drug effects ; immunology ; physiopathology

Mast cells have been regarded for a long time as effector cells in IgE mediated type I reactions and in host defence against parasites. However, they are resident in all environmental exposed tissues and express a wide variety of receptors, suggesting that these cells can also function as sentinels in innate immune responses. Indeed, studies have demonstrated an important role of mast cells during the induction of life-saving antibacterial responses. Furthermore, recent findings have shown that mast cells promote and modulate the development of adaptive immune responses, making them an important hinge of innate and acquired immunity. In addition, mast cells and several mast cell-produced mediators have been shown to be important during the development of allergic airway diseases. In the present review, we will summarize findings on the role of mast cells during the development of adaptive immune responses and highlight their function, especially during the development of allergic asthma.
Animals ; Anti-Infective Agents/pharmacology ; Asthma/*immunology/metabolism ; Cytokines/metabolism ; Histamine/metabolism ; Humans ; Hypersensitivity/*immunology/metabolism ; Immune System ; Immunoglobulin E/immunology ; Leukotrienes/metabolism ; Mast Cells/*cytology ; Mice ; Models, Biological ; Prostaglandins/metabolism ; Tumor Necrosis Factor-alpha/metabolism

In the present work, we have examined the effect of PAF, removal of epithelium, the mechanism of desensitization, and the substances that increases the level of intracellular c-AMP on the differences of mediator release from superfused tracheal strips after passive sensitization with IgG1 versus IgE Ab. In the passive sensitized tracheal tissues, the effect of PAF and the mechanism of desensitization have been examined by PAF antagonist, CV 3988 and DFP, respectively. The epithelium was stripped from one-half of each trachea by mechanical means. Both superfused tracheal tissues were challenged with Ox-Ag. Inhibitors of mediator release were added into a superfused buffer. Hist released was determined by spectrophotofluorometer, and LT by radioimmunoassay. PAF known to mediate the allergic reaction was not released by Ag after both Ab sensitization. Epithelium removal resulted in similar contraction, Hist and LT release after IgG1 Ab activation, but in the IgE Ab activation, epithelium removal resulted in smaller contraction and Hist release. In the L-cysteine and indomethacin pretreatment after two Ab sensitization, epithelium removal decreased the release of Hist and LT. The compound 48/80 pre-challenge and epithelium removal resulted in the increase of Hist release, but in the decrease of LT release after IgG1 or IgE sensitization. The Amount of LT released by Ag after compound 48/80 pre-challenge increased in the absence or presence of epithelium after both Ab sensitization. Mediator release from tissues sensitized with both Abs was not changed by DFP. The responses of inhibitors to prevent the mediator release were more effective on the IgE Ab than on the IgG1 Ab sensitization. These studies suggest that the tracheal epithelium can act to inhibit immune- and non-immune-induced airway responses. Non-immunological responses may in part reflect the role of epithelium as a diffusion barrier and modulator of mediator release. These data also suggest that immunological responses are related to the localization and functional heterogeneity of tissue mast cells.
Animal ; Epithelium/immunology/physiology ; Female ; Guinea Pigs ; *Histamine Release ; *Immunization ; Immunoglobulin E/*immunology ; Immunoglobulin G/*immunology ; Leukotrienes/metabolism ; Mast Cells/immunology ; Support, Non-U.S. Gov't ; Trachea/*immunology/physiology

BACKGROUND AND OBJECTIVES: It is known that various inflammatory mediators released from the eosinophils and mast cells play important roles in the pathogenesis of nasal polyp. Among those mediators, the arachidonic acid has particular importance as a precursor of other mediators. By assaying the tissue concentration of the6-keto-PGF(1alpha), leukotrienes (LTs), and hydroxyeicosatetraenoic acids (HETE) in the nasal polyp, we aimed to investigate the role of arachidonic acid metabolite in the pathogenesis of antrochoanal polyp and nasal polyp associated with chronic paranasal sinusitis. MATERIALS AND METHODS:Three turbinate tissues taken during the septoplasty were served as the control. The experimental group consisted of 3 antrochoanal polyps and 7 inflammatory polyps. The tissue level of the 6-keto-PGF(1alpha), LTC(4), LTD(4), LTE(4), 15-HETE, and 12-HETE were measured using high performance liquid chromatography. RESULTS: The level of 6-keto-PGF(1alpha), LTC4, 15-HETE, 12-HETE were significantly lower in antrochoanal polyp than in the control turbinate. In the inflammatory polyp, the levels of 6-keto-PGF(1alpha) and LTC(4) were lower than the control. However, in the inflammatory polyp, LTD(4) and LTE(4) were detectable, which were not detected in the control turbinate and antrochoanal polyp. CONCLUSION: The results of this study indicate that the decreased arachidonic acid metabolism may underlie the pathogenesis of the antrochoanal polyp. However, in the pathogenesis of inflammatory polyp, the increased production of LTD(4) and LTE(4) may have an important role.
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid ; Arachidonic Acid* ; Chromatography, Liquid ; Eosinophils ; Hydroxyeicosatetraenoic Acids ; Leukotriene C4 ; Leukotrienes ; Mast Cells ; Metabolism ; Nasal Polyps* ; Polyps* ; Sinusitis* ; Turbinates

OBJECTIVETo observe the changing contents of leukotriene B4 ( LTB4 ), leukotriene C4 ( LTC4 ), and leukotriene D4 (LTD4 ) of lung tissue in asthmatic rats, and explore the effect of Shuanglong Capsule (SLC) on it.

METHODSSD rats were randomly divided into the nomal group, asthmatic model group, Dexamethasone group and the high, middle and low dose SLC groups. All rats except those in the normal group were sensitized by ovalbumin and challenged with the antigen, and the contents of LTB4, LTC4 and LTD4 in lung tissue of all the groups were measured by reverse phase-high performance liquid chromatography (RP-HPLC) and compared.

RESULTSThe levels of LTB4, LTC4, and LTD4 of asthmatic rats were significantly higher than those of rats in the normal group. Dexamethasone and SLC at the dose of 8. 27 g/kg or 4. 13 g/kg could significantly inhibit the production of leukotrienes of lung tissue in asthmatic rats (P <0.05).

CONCLUSIONSLC can significantly inhibit the formation of inflammatory medium LTs of lung tissue in asthmatic rats, it may be one of the key mechanisms of SLC in anti-asthma and anti-inflammatory action.

Animals ; Anti-Asthmatic Agents ; pharmacology ; Asthma ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Leukotriene B4 ; metabolism ; Leukotriene C4 ; metabolism ; Leukotriene D4 ; metabolism ; Leukotrienes ; metabolism ; Lung ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Tablets

OBJECTIVETo study the changes of collagen synthesis following mechanical ventilation with different tidal volume and the possible mechanism.

METHODSTwenty-four neonatal Sprague-Dawley rats were randomized to hyperventilation (tidal volume 25 mL/kg), conventional ventilation (tidal volume 10 mL/kg) and no mechanical ventilation (control group) (n=8 each group). They were sacrificed 5 hrs after ventilation. Left lung samples were used for histopathologic examinations and the detection of connective tissue growth factor (CTGF) expression by immunohistochemistry. Right lung samples were used for the detection of expression of procollagenIII mRNA(PcolIII mRNA), cysteinyl leukotriene mRNA(CysLT1 mRNA)and CTGF mRNA by PCR.

RESULTSThe severity of lung injury and fibrosis increased significantly with the increasing tidal volume compared with the control group. Lung CTGF mRNA expression in the hyperventilation group was significantly higher than that in the control group (P<0.05). Lung PcolIII mRNA and CysLT1 mRNA levels increased with the increasing tidal volume when compared with the control group. The differences in PcolIII mRNA and CysLT1 mRNA levels between groups were significant (P<0.05). There was a positive correlation between lung PcolIII mRNA expression and the severity of lung injury (r=0.78,P<0.01). CTGF and CysLT levels were positively correlated with PcolIII expression (r = 0.59,0.86,P<0.01).

CONCLUSIONSMechanical ventilation using different tidal volume leads to different severities of lung injury, followed by the occurrence of lung fibrosis. The degree of lung fibrosis is consistent with the severity of lung injury. CysLT and CTGF may be involved in the development of lung fibrosis.

Animals ; Animals, Newborn ; Collagen Type III ; genetics ; Connective Tissue Growth Factor ; genetics ; Cysteine ; genetics ; Leukotrienes ; genetics ; Lung ; pathology ; Pulmonary Fibrosis ; etiology ; metabolism ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Respiration, Artificial ; adverse effects ; Tidal Volume

OBJECTIVETo investigate the role of cysteinyl leukotriene (CysLT) receptors in the differentiation of rat glioma C6 cells.

METHODSRat glioma C6 cells were treated with the agonist LTD(4), the CysLT(1) receptor antagonist montelukast and the differentiation inducer forskolin. Cell morphology and GFAP protein expression were determined after treatments.

RESULTForskolin (10 μmol/L) induced morphological changes and GFAP protein expression (cell differentiation) in C6 cells, but LTD(4) (0.1-100 nmol/L) did not induce these changes. Montelukast (1 μmol/L) alone did not affect C6 cell differentiation, while it induced the differentiation when combined with the LTD(4) (100 nmol/L).

CONCLUSIONThe CysLT(2) receptor may modulate the differentiation of rat glioma C6 cells.

Acetates ; pharmacology ; Animals ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Colforsin ; pharmacology ; Cysteine ; Glioma ; metabolism ; pathology ; Leukotriene Antagonists ; pharmacology ; Leukotriene D4 ; pharmacology ; Leukotrienes ; Quinolines ; pharmacology ; Rats ; Receptors, Leukotriene ; agonists