Linoleic acid and dihomogammalinolenic acid inhibit leukotriene B4 formation and stimulate the formation of their 15-lipoxygenase products by human neutrophilsin vitro. Evidence of formation of antiinflammatory compounds

1991 ◽  
Vol 33 (3-4) ◽  
pp. 286-291 ◽  
Author(s):  
L. Iversen ◽  
K. Fogh ◽  
G. Bojesen ◽  
K. Kragballe
Keyword(s):  
Linoleic Acid ◽  
Leukotriene B4 ◽  
Lipoxygenase Products ◽  
Dihomogammalinolenic Acid

Microcirculatory disturbance in indomethacin-induced intestinal ulcer

1991 ◽  
Vol 261 (2) ◽  
pp. G213-G219 ◽  
Author(s):  
S. Miura ◽  
M. Suematsu ◽  
S. Tanaka ◽  
H. Nagata ◽  
S. Houzawa ◽  
...  
Keyword(s):  
Intestinal Mucosa ◽  
Venous Blood ◽  
Leukotriene B4 ◽  
Ulcer Formation ◽  
Myeloperoxidase Activity ◽  
Neutrophil Accumulation ◽  
Intestinal Ulcer ◽  
Leukocyte Accumulation ◽  
Lipoxygenase Products ◽  
Microcirculatory Disturbances

Participation of microcirculatory disturbances, especially the role of 5-lipoxygenase products from neutrophils, was investigated in indomethacin (Indo)-induced ulcers of rat small intestine. After Indo treatment (20 mg/kg) in rats, small erosions appeared at 6 h and longitudinal ulcers developed 12 h later. At 6 and 12 h after Indo treatment, severe microcirculatory disturbances were observed under an intravital fluorescence microscope. Significant delay in the clearance and patchy pooling of injected fluorescein isothiocyanate-bovine serum albumin with sludge and stasis were observed in archade vessels of villi of Indo-treated rats. Increased numbers of sticking leukocytes were also detected along submucosal venules in these rats after the infusion of acridine orange. When regional venous blood was collected from the mesentery, a marked increase in neutrophil number and their increased production of oxygen-derived free radicals as determined by chemiluminescence assay were demonstrated at 6 h after Indo treatment. There was also a significant increase in myeloperoxidase activity of the intestinal mucosa at 6 and 12 h after Indo treatment, suggesting a significant neutrophil accumulation at this time. AA-861, a selective inhibitor of 5-lipoxygenase (80 mg/kg), attenuated these microcirculatory changes and neutrophil accumulation in the intestinal mucosa. AA-861 also significantly prevented the formation of intestinal ulcers induced by Indo. However, Indo-induced ulcer formation and leukocyte accumulation in submucosal venules were not attenuated by the treatment of Ono-1078, a potent antagonist of sulfidopeptide leukotrienes. From these observations, it is considered that microcirculatory disturbances, especially leukocyte accumulation and 5-lipoxygenase products, possibly leukotriene B4, may be involved in the development of Indo-induced intestinal ulcer.

scholarly journals Dietary (n-9) Eicosatrienoic Acid from a Cultured Fungus Inhibits Leukotriene B4 Synthesis in Rats and the Effect Is Modified by Dietary Linoleic Acid

1996 ◽  
Vol 126 (6) ◽  
pp. 1534-1540 ◽  
Author(s):  
Leslie G. Cleland ◽  
Robert A. Gibson ◽  
Mark A. Neumann ◽  
Tomohito Hamazaki ◽  
Kengo Akimoto ◽  
...  
Keyword(s):  
Linoleic Acid ◽  
Eicosatrienoic Acid ◽  
Leukotriene B4 ◽  
Dietary Linoleic Acid

scholarly journals Involvement of lipoxygenase in lysophosphatidic acid-stimulated hydrogen peroxide release in human HaCaT keratinocytes

2000 ◽  
Vol 346 (3) ◽  
pp. 751-758 ◽  
Author(s):  
Madhavi SEKHARAM ◽  
Jess M. CUNNICK ◽  
Jie WU
Keyword(s):  
Hydrogen Peroxide ◽  
Lysophosphatidic Acid ◽  
Egf Receptor ◽  
Leukotriene B4 ◽  
Cyclooxygenase Inhibitors ◽  
Ros Generation ◽  
Hacat Cells ◽  
Hacat Keratinocytes ◽  
Lipoxygenase Inhibitors ◽  
Lipoxygenase Products

Although it is now recognized that low levels of reactive oxygen species (ROS) are required for the mitogenic response, mitogen-induced signalling pathways that regulate ROS generation in non-phagocytic cells remain largely uncharacterized. Using a real-time assay for measuring hydrogen peroxide (H2O2) formation, we analysed H2O2 release in human HaCaT keratinocytes in response to lysophosphatidic acid (LPA), a mitogen for keratinocytes. LPA rapidly increased H2O2 release in HaCaT cells. Unlike LPA-induced mitogen-activated protein (MAP) kinase activation, LPA-stimulated H2O2 release was independent of the tyrosine kinase activity of the epidermal growth factor (EGF) receptor. Calcium chelators, phospholipase A2 inhibitors, and lipoxygenase inhibitors effectively blocked LPA-stimulated H2O2 release, whereas cyclooxygenase inhibitors were without effect. Addition of 5-lipoxygenase products 5-hydroperoxyeicosatetraenoic acid (5-HPETE) and leukotriene B4, but not 5-hydroxyeicosatetraenoic acid (5-HETE) and leukotriene C4, restored LPA-stimulated H2O2 release in cells treated with the lipoxygenase inhibitors nordihydroguaiaretic acid and Zileuton. These results suggest that the lipoxygenase products 5-HPETE and leukotriene B4 are required for LPA-stimulated H2O2 release in HaCaT cells.

Formation of leukotriene B4 and monohydroxy acids in slices of porcine thyroid gland

1988 ◽  
Vol 117 (4) ◽  
pp. 463-469 ◽  
Author(s):  
Björn Odlander ◽  
Hans-Erik Claesson
Keyword(s):  
Arachidonic Acid ◽  
Thyroid Gland ◽  
Time Course ◽  
Leukotriene B4 ◽  
Eicosatetraenoic Acid ◽  
A 23187 ◽  
Lipoxygenase Products

Abstract. Slices of porcine thyroid gland were incubated with arachidonic acid and ionophore A 23187. This led to the formation of 5-hydroxy-eicosatetraenoic acid (5-HETE), 12-HETE, 15-HETE and leukotriene B4 (LTB4). Time course studies demonstrated that levels of detected LTB4 reached a plateau after 30 min and that in parallel with the synthesis of this compound, greater amounts of 5-HETE was formed. The present results demonstrate the formation of lipoxygenase products in the porcine thyroid gland, indicating possible physiological/pathophysiological roles for these compounds in this organ.

Human alveolar macrophage arachidonic acid metabolism

1988 ◽  
Vol 254 (6) ◽  
pp. C809-C815 ◽  
Author(s):  
G. P. Brown ◽  
M. M. Monick ◽  
G. W. Hunninghake
Keyword(s):  
Arachidonic Acid ◽  
Alveolar Macrophages ◽  
Biological Effects ◽  
Leukotriene B4 ◽  
Arachidonic Acid Metabolism ◽  
Ionophore A23187 ◽  
Lipoxygenase Pathway ◽  
Cyclooxygenase Inhibition ◽  
Human Alveolar Macrophage ◽  
Lipoxygenase Products

Metabolites of arachidonic acid are potent modulators of many biological events, and their release from macrophages appears to play an important role in immune and inflammatory processes. In addition, metabolites of the cyclooxygenase or lipoxygenase pathway exhibit distinct biological effects. We used a method to determine if human alveolar macrophages (HAM) could be selectively activated to release products of cyclooxygenase or lipoxygenase pathway of arachidonic acid. HAM obtained by bronchoalveolar lavage from individuals were [3H]arachidonic acid labeled and then stimulated with lipopolysaccharide (LPS) or Ca ionophore A23187. Essentially no arachidonate metabolites were released by unstimulated cells. LPS caused dose- and time-dependent release of arachidonate and only cyclooxygenase products; no lipoxygenase products were detected, even in presence of cyclooxygenase inhibition. Metabolites released in response to LPS included thromboxane B2, prostaglandins D2, F2a, E2, and hydroxyheptadecatrienoic acid. A23187 caused a rapid release of arachidonate and 5-lipoxygenase products, leukotriene B4 and 5-hydroxyeicosatetraenoic acid; no cyclooxygenase inhibition. This demonstrates that HAM are specifically activated to release metabolites derived from cyclooxygenase or lipoxygenase pathway of arachidonic acid. Additionally, shunting down an alternate pathway is not induced by use of inhibitors of either pathway. This suggests alveolar macrophages may enhance or suppress various inflammatory or immune processes in lung, in part, by selective release of various derivatives of arachidonic acid.

scholarly journals Airway Microbiome and Serum Metabolomics Analysis Identify Differential Candidate Biomarkers in Allergic Rhinitis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yuze Yuan ◽  
Chao Wang ◽  
Guoqiang Wang ◽  
Xiaoping Guo ◽  
Shengyu Jiang ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Linoleic Acid ◽  
Acid Metabolism ◽  
Prediction Models ◽  
Inferior Turbinate ◽  
Leukotriene B4 ◽  
Arachidonic Acid Metabolism ◽  
Prostaglandin D2 ◽  
Serum Samples ◽  
Serum Metabolomics

Allergic rhinitis (AR) is a common heterogeneous chronic disease with a high prevalence and a complex pathogenesis influenced by numerous factors, involving a combination of genetic and environmental factors. To gain insight into the pathogenesis of AR and to identity diagnostic biomarkers, we combined systems biology approach to analyze microbiome and serum composition. We collected inferior turbinate swabs and serum samples to study the microbiome and serum metabolome of 28 patients with allergic rhinitis and 15 healthy individuals. We sequenced the V3 and V4 regions of the 16S rDNA gene from the upper respiratory samples. Metabolomics was used to examine serum samples. Finally, we combined differential microbiota and differential metabolites to find potential biomarkers. We found no significant differences in diversity between the disease and control groups, but changes in the structure of the microbiota. Compared to the HC group, the AR group showed a significantly higher abundance of 1 phylum (Actinobacteria) and 7 genera (Klebsiella, Prevotella and Staphylococcus, etc.) and a significantly lower abundance of 1 genus (Pelomonas). Serum metabolomics revealed 26 different metabolites (Prostaglandin D2, 20-Hydroxy-leukotriene B4 and Linoleic acid, etc.) and 16 disrupted metabolic pathways (Linoleic acid metabolism, Arachidonic acid metabolism and Tryptophan metabolism, etc.). The combined respiratory microbiome and serum metabolomics datasets showed a degree of correlation reflecting the influence of the microbiome on metabolic activity. Our results show that microbiome and metabolomics analyses provide important candidate biomarkers, and in particular, differential genera in the microbiome have also been validated by random forest prediction models. Differential microbes and differential metabolites have the potential to be used as biomarkers for the diagnosis of allergic rhinitis.

scholarly journals Elevated Plasma Level of Leukotrienes in Bronchial Asthma Patients: A Possible Clinical Relevance

1994 ◽  
Vol 12 (2) ◽  
pp. 117-122 ◽  
Author(s):  
Mahmoud Mansour ◽  
Nabil Farouk ◽  
Abbas El Maragy ◽  
Ibrahim Radwan ◽  
Omar El-Ahmady
Keyword(s):  
Bronchial Asthma ◽  
Lipid Extraction ◽  
Leukotriene B4 ◽  
Mean Value ◽  
Asthmatic Patients ◽  
Healthy Donors ◽  
Lipoxygenase Products ◽  
Asthma Patients ◽  
The Mean ◽  
Chemical Mediators

Plasma from bronchial asthma patients and healthy controls was investigated for the content of lipoxygenase products. After lipid extraction using SEP-PAK C18Cartridges, the lipoxygenase products were measured by Enzyme-Immunoassay. Elevated chemotactic B4 was found in plasma from asthmatic patients with mean value (483±75) pmoUL, while the mean value in normal healthy donors was (140± 12.1) pmol/L (M±SE). The levels of spasmogenic cysteinyl containing leukotrienes were also very high in the bronchial asthma patients. Elevations of leukotriene B4and cysteinyl containing leukotrienes were detected during attacks of bronchial asthma. These results suggest that leukotriene B4 may be important in the pathogenesis of bronchial asthma and confirmed that peptidoleukotrienes playa role as chemical mediators during the asthmatic attack.

Differential effect of 5- and 15-lipoxygenase products on ischemically sensitive abdominal visceral afferents

1995 ◽  
Vol 269 (1) ◽  
pp. H96-H105 ◽  
Author(s):  
H. L. Pan ◽  
G. L. Stahl ◽  
J. C. Longhurst
Keyword(s):  
Receptive Field ◽  
Impulse Activity ◽  
Leukotriene B4 ◽  
Visceral Afferents ◽  
Single Unit Activity ◽  
Tetraenoic Acid ◽  
Mechanical Threshold ◽  
Lipoxygenase Products ◽  
C Fiber ◽  
The Right

The effects of 5- and 15-lipoxygenase products, leukotriene B4 (LTB4) and (8R,15S)-dihydroxyeicosa(5E-9,11,13Z)tetraenoic acid (8R,15S-diHETE), on ischemically sensitive abdominal visceral C fiber afferents were evaluated, because this system is important in sensitizing cutaneous afferents. Single-unit activity of abdominal visceral C fiber afferents was recorded from the right thoracic sympathetic chain of anesthetized cats during 5 min of ischemia. Inhibition of 5-lipoxygenase with WY-50295 tromethamine (5 mg/kg iv) augmented the impulse activity from 0.48 +/- 0.15 to 0.79 +/- 0.24 impulses/s (P < 0.05) in seven ischemically sensitive afferents. Conversely, topical application of LTB4 (125 ng) directly onto the receptive field attenuated impulse activity of 10 ischemically sensitive C fiber afferents from 0.82 +/- 0.23 to 0.42 +/- 0.10 impulses/s (P < 0.05). In additional cats, application of 8R,15S-diHETE (125 ng) onto the receptive field augmented the impulse activity of nine ischemically sensitive C fiber afferents (from 0.48 +/- 0.15 to 0.70 +/- 0.15 impulses/s, P < 0.05) and significantly decreased the mechanical threshold of these nine afferents, whereas application of 8S,15S-diHETE (125 ng), a stereoisomer of 8R,15S-diHETE, attenuated the impulse activity from 0.77 +/- 0.48 to 0.45 +/- 0.13 impulses/s (P < 0.05) in six additional ischemically sensitive C fiber afferents. In animals pretreated with aspirin (50 mg/kg iv, n = 6) or 8S,15S-diHETE (125 ng, n = 6), WY-50295 tromethamine (5 mg/kg iv) still potentiated the impulse activity of ischemically sensitive C fiber afferents. These data indicate that 8R,15S-diHETE interacts with stereospecific receptors to sensitize, whereas LTB4 reduces, the response of abdominal visceral afferents to ischemia. Furthermore the data suggest that the augmented response of afferents to abdominal ischemia after inhibition of 5-lipoxygenase is, at least in part, independent of shunting to the cyclooxygenase or 15-lipoxygenase system.

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