Prostaglandins Inhibit 5-Lipoxygenase-Activating Protein Expression and Leukotriene B4 Production from Dendritic Cells Via an IL-10-Dependent Mechanism

Harizi, Hedi; Juzan, M.; Moreau, Jean-François; Gualde, Norbert

doi:10.4049/jimmunol.170.1.139

Cited by 73 publications

(89 citation statements)

References 55 publications

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“…Although we have shown that enhanced PGE 2 production inhibits initial LTB 4 production, it is likely that 5-LOX activity is not completely inhibited in COX-2 overexpressers but that the mass ratio of products has heavily shifted toward prostaglandin signaling. We cannot rule out, however, other indirect effects that PGE 2 might have on LTB 4 production such as the inhibition of 5-LOX-activating protein (FLAP) via an IL-10-dependent mechanism as was seen in dendritic cells (12).…”

Section: Discussionmentioning

confidence: 99%

5-Lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers

Green

Stockton²,

Johnson³

et al. 2004

American Journal of Physiology-Cell Physiology

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involves multiple cell signaling pathways, including those regulating cell-extracellular matrix adhesion. Previous work demonstrated that arachidonate oxidation to leukotriene B4 (LTB4) by 5-lipoxygenase (5-LOX) signals fibroblast spreading on fibronectin, whereas cyclooxygenase-2 (COX-2)-catalyzed prostaglandin E2 (PGE2) formation facilitates subsequent cell migration. We investigated arachidonate metabolite signaling in wound closure of perturbed NIH/3T3 fibroblast monolayers. We found that during initial stages of wound closure (0 -120 min), all wound margin cells spread into the wound gap perpendicularly to the wound long axis. At regular intervals, between 120 and 300 min, some cells elongated to project across the wound and meet cells from the opposite margin, forming distinct cell bridges spanning the wound that act as foci for later wound-directed cell migration and resulting closure. 5-LOX inhibition by AA861 demonstrated a required LTB4 signal for initial marginal cell spreading and bridge formation, both of which must precede wound-directed cell migration. 5-LOX inhibition effects were reversible by exogenous LTB4. Conversely, COX inhibition by indomethacin reduced directed migration into the wound but enhanced early cell spreading and bridge formation. Exogenous PGE2 reversed this effect and increased cell migration into the wound. The differential effects of arachidonic acid metabolites produced by LOX and COX were further confirmed with NIH/3T3 fibroblast cell lines constitutively over-and underexpressing the 5-LOX and COX-2 enzymes. These data suggest that two competing oxidative enzymes in arachidonate metabolism, LOX and COX, differentially regulate sequential aspects of fibroblast wound closure in vitro.

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Section: Discussionmentioning

confidence: 99%

5-Lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers

Green

Stockton²,

Johnson³

et al. 2004

American Journal of Physiology-Cell Physiology

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“…Eicosanoids interfere with each other's production both in vivo (23) or in vitro (38). Systemic OVA sensitization alone increased PGE 2 production in the lung, and LTRA treatment further enhanced it (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…3C). Harizi et al (38) previously reported that LTB 4 does not affect COX expression and PGE 2 production from macrophages. In addition, in our in vivo experiments, the cells most responsible for PGE 2 production seem to be macrophages, because cells in BALF mainly consisted of alveolar macrophages (Table ⌱), and PGE synthase mainly exists in macrophages, at least in mice (39).…”

Section: Discussionmentioning

confidence: 99%

A Novel Role of Cysteinyl Leukotrienes to Promote Dendritic Cell Activation in the Antigen-Induced Immune Responses in the Lung

Okunishi

Dohi

Nakagome

et al. 2004

The Journal of Immunology

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Although the critical role of cysteinyl leukotrienes (cysLTs) in the inflammation, especially eosinophilic lung inflammation, in asthma has been well documented, their role in the early stage of Ag-specific immune response has not been completely clarified. In the present study, with a mouse model of asthma and in vitro studies we demonstrated that cysLTs potentiated dendritic cell (DC) functions such as Ag-presenting capacity and cytokine production. The cysLT-1 receptor antagonist (LTRA) strongly suppressed the activation of these DC functions and led to inhibition of subsequent not only Th2, but also Th1, responses in the early stage of immune response. Moreover, treatment with LTRA during the early stage of the immune response potently suppressed the development of Ag inhalation-induced eosinophilic airway inflammation, mucus production, and airway hyper-reactivity in vivo. Treatment with LTRA significantly increased PGE2 production in the lung, and treatment with the cyclooxygenase inhibitor indomethacin abolished LTRA’s suppressive effect on DCs and deteriorated the Th2 and Th1 responses and airway inflammation. With in vitro studies, we also confirmed that cysLTs production by DCs increased with LPS stimulation, and that LTRA directly suppressed the alloantigen-presenting capacity of DCs. These results suggested that cysLTs potentiate DC functions both in vivo and in vitro, and that LTRA could be beneficial to suppress the initial immune response in many immune-mediated disorders beyond asthma.

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“…PGE 2 has been reported to have other actions, e.g. suppressing dendritic cell leukotriene B 4 secretion by an IL-10-dependent mechanism (22) . The enzyme pathways that metabolise arachidonic acid also metabolise n-3 PUFA such as EPA to 3-series PG and 5-series leukotrienes that possess biological activity, albeit less potent than arachidonic acid metabolites.…”

Section: Pufamentioning

confidence: 99%

Session 1: Allergic disease Nutrition as a potential determinant of asthma

Devereux

2009

Proc. Nutr. Soc.

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Asthma is characterised by chronic lung airway inflammation, increased airway responsiveness and variable airflow obstruction. In Westernised countries asthma is a public health concern because of its prevalence, associated ill health and high societal and healthcare costs. In recent decades there has been a marked increase in asthma prevalence, particularly in Westernised countries. It has been proposed that changing diet has contributed to the increase in asthma. Several dietary hypotheses exist; the first relates the increase in asthma to declining dietary antioxidant intake, the second to decreased intake of long-chainn-3 PUFA and increasing intake ofn-6 PUFA. Vitamin D supplementation and deficiency have also been hypothesised to have contributed to the increase in asthma. Observational studies have reported associations between asthma and dietary antioxidants (vitamin E, vitamin C, carotenoids, Se, flavonoids, fruit), lipids (PUFA, butter, margarine, fish) and vitamin D. However, supplementing the diets of adults with asthma with antioxidants and lipids has minimal, if any, clinical benefit. There is growing interest in the possibility that childhood asthma is influenced by maternal diet during pregnancy, with studies highlighting associations between childhood asthma and maternal intake of some nutrients (vitamin E, vitamin D, Se, PUFA) during pregnancy. It has been suggested that maternal diet during pregnancy influences fetal airway and/or immune development. Further intervention studies are needed to establish whether modification of maternal nutrient intake during pregnancy can be used as a healthy low-cost public health measure to reduce the prevalence of childhood asthma.

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Prostaglandins Inhibit 5-Lipoxygenase-Activating Protein Expression and Leukotriene B4 Production from Dendritic Cells Via an IL-10-Dependent Mechanism

Cited by 73 publications

References 55 publications

5-Lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers

5-Lipoxygenase and cyclooxygenase regulate wound closure in NIH/3T3 fibroblast monolayers

A Novel Role of Cysteinyl Leukotrienes to Promote Dendritic Cell Activation in the Antigen-Induced Immune Responses in the Lung

Session 1: Allergic disease Nutrition as a potential determinant of asthma

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