Retinoic acid and host-pathogen interactions: effects on inducible nitric oxide synthase in vivo

Devaux, Yvan; Grosjean, Sandrine; Seguin, Carole; David, C.; Dousset, B; Zannad, Faı̈ez; Meistelman, Claude; Talancé, Nicole de; Mertès, Paul-Michel; Ungureanu-Longrois, Dan

doi:10.1152/ajpendo.2000.279.5.e1045

Cited by 28 publications

(28 citation statements)

References 43 publications

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“…RA (Roche, Kaiseraugst, Switzerland) was dissolved in the vehicle (liquid paraffin) at a final concentration of 10 mg/ml. RA-supplemented (RA-S) mice received daily intraperitoneal injections of RA (10 mg/kg body weight) for 5 consecutive days in a manner similar to that previously described (37). Control mice received an equal volume of the vehicle.…”

Section: Methodsmentioning

confidence: 99%

Retinoid Levels Influence Enterohemorrhagic Escherichia coli Infection and Shiga Toxin 2 Susceptibility in Mice

et al. 2014

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e Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that produces Shiga toxin (Stx) and causes hemorrhagic colitis. Under some circumstances, Stx produced within the intestinal tract enters the bloodstream, leading to systemic complications that may cause the potentially fatal hemolytic-uremic syndrome. Although retinoids like vitamin A (VA) and retinoic acid (RA) are beneficial to gut integrity and the immune system, the effect of VA supplementation on gastrointestinal infections of different etiologies has been controversial. Thus, the aim of this work was to study the influence of different VA status on the outcome of an EHEC intestinal infection in mice. We report that VA deficiency worsened the intestinal damage during EHEC infection but simultaneously improved survival. Since death is associated mainly with Stx toxicity, Stx was intravenously inoculated to analyze whether retinoid levels affect Stx susceptibility. Interestingly, while VA-deficient (VA-D) mice were resistant to a lethal dose of Stx2, RA-supplemented mice were more susceptible to it. Given that peripheral blood polymorphonuclear cells (PMNs) are known to potentiate Stx2 toxicity, we studied the influence of retinoid levels on the absolute number and function of PMNs. We found that VA-D mice had decreased PMN numbers and a diminished capacity to produce reactive oxygen species, while RA supplementation had the opposite effect. These results are in line with the well-known function of retinoids in maintaining the homeostasis of the gut but support the idea that they have a proinflammatory effect by acting, in part, on the PMN population.

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Section: Methodsmentioning

confidence: 99%

Retinoid Levels Influence Enterohemorrhagic Escherichia coli Infection and Shiga Toxin 2 Susceptibility in Mice

et al. 2014

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“…A low dose LPS-mediated activation of the NOS2 pathway (18,19) was obtained by i.p. injection of LPS (6 mg/kg body weight (bw)) to all rats, except those of the control group (n ϭ 4) that received 500 l of 0.9% NaCl i.p.…”

Section: Experimental Protocolsmentioning

confidence: 99%

“…Under these circumstances, NOS2 inhibitors might have beneficial effects on host survival (typically high LPS doses in rodent models; Ref. 18). Other types of stimuli, such as the low dose LPS used in the present study, result in NOS2 induction and low level/absent COX-2 induction with NO or ONOO Ϫ , resulting in increased COX-1-derived end products.…”

Section: Beneficial and Deleterious Effects Of Nos2 Inhibitorsmentioning

confidence: 99%

Lipopolysaccharide-Induced Increase of Prostaglandin E2 Is Mediated by Inducible Nitric Oxide Synthase Activation of the Constitutive Cyclooxygenase and Induction of Membrane-Associated Prostaglandin E Synthase

Devaux¹,

Seguin²,

Grosjean

et al. 2001

The Journal of Immunology

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NO produced by the inducible NO synthase (NOS2) and prostanoids generated by the cyclooxygenase (COX) isoforms and terminal prostanoid synthases are major components of the host innate immune and inflammatory response. Evidence exists that pharmacological manipulation of one pathway could result in cross-modulation of the other, but the sense, amplitude, and relevance of these interactions are controversial, especially in vivo. Administration of 6 mg/kg LPS to rats i.p. resulted 6 h later in induction of NOS2 and the membrane-associated PGE synthase (mPGES) expression, and decreased constitutive COX (COX-1) expression. Low level inducible COX (COX-2) mRNA with absent COX-2 protein expression was observed. The NOS2 inhibitor aminoguanidine (50 and 100 mg/kg i.p.) dose dependently decreased both NO and prostanoid production. The LPS-induced increase in PGE2 concentration was mediated by NOS2-derived NO-dependent activation of COX-1 pathway and by induction of mPGES. Despite absent COX-2 protein, SC-236, a putative COX-2-specific inhibitor, decreased mPGES RNA expression and PGE2 concentration. Ketoprofen, a nonspecific COX inhibitor, and SC-236 had no effect on the NOS2 pathway. Our results suggest that in a model of systemic inflammation characterized by the absence of COX-2 protein expression, NOS2-derived NO activates COX-1 pathway, and inhibitors of COX isoforms have no effect on NOS2 or NOS3 (endothelial NOS) pathways. These results could explain, at least in part, the deleterious effects of NOS2 inhibitors in some experimental and clinical settings, and could imply that there is a major conceptual limitation to the use of NOS2 inhibitors during systemic inflammation.

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“…31 Moreover, sentrin/SUMO-specific protease1 (SENP1) plays a key role in the regulation of HIF1α stability. 32 Although the effects of ATRA on the production of nitric oxide, a donor for nitrosylation, are controversial, 33,34 we still investigated whether the S-nitrosylation or deSUMOylation of HIF-1α protein contributes to the ATRA-induced increase of HIF-1α protein. We found that L-NAME and 1400W, potent inhibitors of nitric oxide synthases, 31 failed to inhibit the ATRA-induced increase of HIF-1α protein in complete culture medium, while SENP1 expression was slightly upregulated during ATRA treatment (data not shown).…”

mentioning

confidence: 99%

Accumulation of hypoxia-inducible factor-1 protein and its role in the differentiation of myeloid leukemic cells induced by all-trans retinoic acid

Zhang

Wang²,

Huang³

et al. 2008

Haematologica

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BackgroundThe clinical activities of all-trans retinoic acid in the treatment of acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia, have triggered extensive studies aimed at defining the mechanisms by which this compound induces differentiation of leukemic cells. Recent studies show that hypoxia-inducible factor-1α (HIF-1α) contributes to the differentiation of acute myeloid leukemia cells via transcriptional activity-independent mechanisms. We investigated whether all-trans retinoic acid affects HIF-1α protein and whether this has a role in all-trans retinoic acid-induced differentiation.

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Retinoic acid and host-pathogen interactions: effects on inducible nitric oxide synthase in vivo

Cited by 28 publications

References 43 publications

Retinoid Levels Influence Enterohemorrhagic Escherichia coli Infection and Shiga Toxin 2 Susceptibility in Mice

Retinoid Levels Influence Enterohemorrhagic Escherichia coli Infection and Shiga Toxin 2 Susceptibility in Mice

Lipopolysaccharide-Induced Increase of Prostaglandin E2 Is Mediated by Inducible Nitric Oxide Synthase Activation of the Constitutive Cyclooxygenase and Induction of Membrane-Associated Prostaglandin E Synthase

Accumulation of hypoxia-inducible factor-1 protein and its role in the differentiation of myeloid leukemic cells induced by all-trans retinoic acid

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