15-hydroxy-5-8-11-13-eicosatetraenoic-acid and Chronic-Disease

We evaluated the levels of 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE] and the expression of 15-lipoxygenase (15-LO) mRNA in induced sputum obtained from 10 control and 15 chronic bronchitis subjects. 15(S)-HETE was evaluated by reverse phase high-performance liquid chromatography separation followed by specific RIA. 15-LO mRNA expression was determined by primed in situ labeling. The levels of both soluble and cell-associated 15(S)-HETE resulted significantly higher in chronic bronchitis than in control subjects. The percentage of cells expressing 15-LO mRNA was significantly higher in chronic bronchitis than in control subjects (P < 0.01). Double staining for specific cell type markers and 15-LO mRNA showed macrophages and neutrophils positive for 15-LO, whereas similar staining of peripheral blood neutrophils did not show evidence for 15-LO expression, suggesting that expression of 15-LO in neutrophils takes place on migration into the airways. Because 15(S)-HETE inversely correlated with the percentage of neutrophils in sputum of chronic bronchitis subjects, we studied the effect of 15(S)-HETE on leukotriene B(4) (LTB(4)) production in vitro and evaluated the concentration of LTB(4) in induced sputum and the contribution of LTB(4) to the chemotactic activity of induced sputum samples ex vivo. The results obtained indicate that macrophages and neutrophils present within the airways of chronic bronchitis subjects express 15-LO mRNA; increased basal levels of 15(S)-HETE may contribute to modulate, through the inhibition of 5-lipoxygenase metabolites production, neutrophil infiltration and airway inflammation associated with chronic bronchitis.

Topics: Adult; Aged; Arachidonate 15-Lipoxygenase; Bronchitis; Cell Count; Cell Survival; Cells, Cultured; Chemotaxis, Leukocyte; Chronic Disease; Humans; Hydroxyeicosatetraenoic Acids; Immunohistochemistry; In Situ Hybridization; Ionophores; Leukotriene Antagonists; Leukotriene B4; Lung Diseases, Obstructive; Macrophages; Middle Aged; Neutrophils; RNA, Messenger; Sputum

Our laboratory has previously demonstrated that 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) is involved in hypoxic pulmonary arterial hypertension. Chronic hypoxia-induced vascular inflammation has been considered as an important stage in the development of pulmonary arterial hypertension. Here, we determined the contribution of 15-HETE in the hypoxia-induced pulmonary vascular inflammation.. Chronic hypoxia-induced monocyte/macrophage infiltration and the expressions of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed in hypoxic rat model and cultured pulmonary arterial endothelium cells using immunochemistry methods. We found that monocyte/macrophage infiltration and the expressions of intercellular adhesion molecules under hypoxia were markedly inhibited by 15-HETE inhibitors or 15-LO1/2 small interfering RNA. In addition, exogenous 15-HETE enhanced the expression of both adhesion molecules in pulmonary arterial endothelium cells in a time-dependent manner. Hypoxia-induced 15-LO1/2 expression in rat pulmonary arterial endothelium cells was significantly abolished by nuclear factor-κB inhibitors. Meanwhile, nuclear factor-κB activity was enhanced prominently by the 15-LO1/2 product, 15-HETE, suggesting a positive feedback mechanism.. Taken together, our results suggest that chronic hypoxia promotes monocyte infiltration into the vasculature and adhesion molecules upregulation in pulmonary arterial endothelium cells via a positive interaction between 15-LO/15-HETE and nuclear factor-κB. Our study revealed a novel mechanism underlying hypoxia-induced pulmonary arterial inflammation and suggested new therapeutic strategies targeting 15-LO/15-HETE and nuclear factor-κB in the treatment of pulmonary arterial hypertension.

Topics: Animals; Arachidonate 15-Lipoxygenase; Arteritis; Cells, Cultured; Chronic Disease; Hydroxyeicosatetraenoic Acids; Hypoxia; Intercellular Adhesion Molecule-1; Male; Monocytes; NF-kappa B; Pulmonary Artery; Rats; Rats, Wistar; Vascular Cell Adhesion Molecule-1

Bronchial epithelial cells are the first cells to come into contact with inhaled pneumoallergens. It has been suggested that these cells may play an important role in the allergic response, and indeed bronchial epithelial cells of some atopic asthmatic subjects have been shown to express the low-affinity receptor for IgE on their surface. In this report we demonstrate, using bronchial biopsies, that bronchial epithelial cells of some asthmatic subjects express both the alpha and gamma chains of the high-affinity receptor for IgE (Fcepsilon RI) on their surface and that they are capable of fixing IgE. Second, using reverse transcription-polymerase chain reaction, we show that both control and asthmatic subjects have messenger RNA for Fcepsilon RI. Finally, we demonstrate that this receptor may be functional since stimulation of the cells with the antibody to the alpha chain of Fcepsilon RI results in the liberation of 15-hydroxyeicosatetraenoic acid from epithelial cells of asthmatic, but not control, subjects or subjects suffering from chronic bronchitis. These data suggest that bronchial epithelial cells from at least some asthmatic subjects express a functional high-affinity receptor for IgE and it is therefore possible that these cells may be able to interact directly with inhaled allergens.

Topics: Adolescent; Adult; Aged; Asthma; Bronchi; Bronchitis; Chronic Disease; Epithelial Cells; Gene Expression; Histamine Release; Humans; Hydroxyeicosatetraenoic Acids; Immunoenzyme Techniques; Immunoglobulin E; Middle Aged; Receptors, IgE; RNA, Messenger

Patients with chronic facial pain including those with facial arthromyalgia (TMJ dysfunction syndrome) were investigated for evidence of abnormal systemic and intra-articular free radical activity. Chronic facial pain patients showed significantly raised serum 2,3-dihydroxybenzoic acid after an oral dose of 1.2 g of aspirin which indicates increased systemic free radical activity. This was reflected in the TMJ aspirates of the facial arthromyalgia patients which contained thiobarbituric acid-reactive substance (TBA-RS) which is also a product of free radical activity. The synovial aspirates also contained high levels of the hyperalgesic eicosanoid 15-HETE. However, there was no difference between the painful and symptom-free joints, which suggested that in part the clinical features are probably determined by asymmetrical masticatory function or as yet unknown algesic factors such as local cytokine production.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Case-Control Studies; Chronic Disease; Cytokines; Dinoprostone; Facial Pain; Female; Free Radicals; Gentisates; Humans; Hydroxybenzoates; Hydroxyeicosatetraenoic Acids; Iron Chelating Agents; Leukotriene B4; Male; Mastication; Middle Aged; Reactive Oxygen Species; Synovial Fluid; Temporomandibular Joint; Temporomandibular Joint Dysfunction Syndrome; Thiobarbituric Acid Reactive Substances

The biochemical changes underlying the clinical manifestations of psoriasis are unknown. Certain chemotactic eicosanoids derived from arachidonic acid metabolism have been suggested to play important roles in psoriasis, because of their presence in lesional psoriatic skin and their ability to elicit skin inflammation and to stimulate epidermal proliferation. The purpose of the present study was to elucidate which eicosanoids might be involved in the early phases of the inflammatory processes of psoriasis. Eicosanoids were analyzed in scale and in lesional skin without scale both in acute guttate and chronic plaque psoriatic lesions. Methods for identification of eicosanoids included reversed-phase high-performance liquid chromatography combined with radioimmunoassay. Leukotriene B4 was present in both acute guttate and chronic plaque skin lesions in biologically active amounts (acute guttate lesions: 18.7 +/- 7.1 ng/g wet tissue in scale and 3.2 +/- 1.5 ng/g wet tissue in lesional skin without scale; chronic plaque lesions: 33.1 +/- 9.7 ng/g wet tissue in scale and 5.3 +/- 2.0 ng/g wet tissue in lesional skin without scale). 12- and 15-hydroxy-eicosatetraenoic acid (HETE) reached biologically active concentrations only in scale of chronic plaque lesions (1,512 +/- 282 and 1,441 +/- 411 ng/g wet tissue, respectively). The level of prostaglandin E2 in chronic plaque lesions was similar to the level in normal skin, while the level in acute guttate lesions was increased twofold (71.0 +/- 14.8 ng/g wet tissue). These results demonstrate that leukotriene B4, but not 12-HETE, is present in acute guttate psoriatic skin lesions in concentrations able to exert biologic effects. Leukotriene B4 may therefore participate in inflammatory changes of acute psoriasis.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Acute Disease; Chromatography, High Pressure Liquid; Chronic Disease; Dinoprostone; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Psoriasis; Radioimmunoassay; Skin