Modulation of Macrophage Nitric Oxide Production by Prostaglandin D2

Bellows, Charles F.; Alder, Adam C.; Wludyka, Peter; Jaffe, Bernard M.

doi:10.1016/j.jss.2005.08.017

Cited by 10 publications

(18 citation statements)

References 23 publications

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“…As expected, increased phagocytosis of PGD 2 -MS was accompanied by the activation of the transcription factor NF-jB, and increased production of NO, TNF-a, and IL-1b. This is in contrast to previous results which reported that exogenous PGD 2 increased the levels of IL-1b but decreased NO and TNF-a production (Bellows et al, 2006;Sandig et al, 2007;Zayed et al, 2010). It is hypothesized that these contradictory data are due to the different cell types used in the studies: AMs, the macrophage-like cell line RAW, and peritoneal macrophages.…”

Section: Discussioncontrasting

confidence: 85%

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Pereira

Bitencourt

Santos

et al. 2015

European Journal of Pharmaceutical Sciences

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Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

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Section: Discussioncontrasting

confidence: 85%

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Pereira

Bitencourt

Santos

et al. 2015

European Journal of Pharmaceutical Sciences

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“…As the authors admitted, these in vitro findings did not reflect the amount of PGD 2 release in vivo or the fact that the niacin flush occurs within a few minutes in humans (Meyers et al, 2007). In contrast, PGD 2 was reported to decrease macrophage production of the potent vasodilator nitric oxide (Bellows et al, 2006). Other reports indicated that nicotinic acid increased expression of prostanoid synthase in epidermal Langerhans cells; depletion of these cells, but not macrophages, eliminated nicotinic acid-induced flushing (Benyó et al, 2006).…”

Section: Discussionmentioning

confidence: 93%

Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

Papaliodis

Boucher²,

Kempuraj³

et al. 2008

J Pharmacol Exp Ther

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Niacin lowers serum cholesterol, low-density lipoprotein, and triglycerides, and it raises high-density lipoprotein. However, most patients experience cutaneous warmth and vasodilation (flush). Acetylsalicylic acid (ASA) can reduce this flush, presumably by decreasing prostaglandin D 2 (PGD 2 ) release from macrophages. Here, we show that methylnicotinate induces significant PGD 2 release from human mast cells and serotonin from human platelets. Intradermal injection of methylnicotinate induces rat skin vasodilation and vascular permeability. Niacin increases plasma PGD 2 and serotonin in a rat model of flush. The phenothiazine prochlorperazine, the H 1 , serotonin receptor antagonist cyproheptadine, and the specific serotonin receptor-2A antagonist ketanserin inhibit niacin-induced temperature increase by 90% (n ϭ 5, p Ͻ 0.05), 90 and 50% (n ϭ 3, p Ͻ 0.05), and 85% (n ϭ 6, p ϭ 0.0008), respectively, in this animal model. These results indicate that niacin-induced flush involves both PGD 2 and serotonin, suggesting that drugs other than ASA are required to effectively inhibit niacin-induced flush.

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“…However, previous investigations have indicated that PGD 2 is an intermediate in agonist-stimulated NO release, which eventually increases cGMP levels [23,24]. To determine whether BW245c increases cyclic nucleotide levels in nasal mucosa, we measured cAMP and cGMP levels in nasal mucosa after incubation for 5 min with BW245c (10 –6 M ).…”

Section: Resultsmentioning

confidence: 99%

“…NO is known to be a vasodilatory factor and NO-induced vasodilatation is associated with an increase in cGMP as a second messenger. PGD 2 has been reported to be an intermediate in agonist-stimulated NO release in rabbit skin [23] and bovine coronary arteries [24]. Therefore, we had considered that PGD 2 -induced relaxation of the nasal mucosa would be caused by cGMP.…”

Section: Discussionmentioning

confidence: 99%

The Potential Role of Prostaglandin D<sub>2</sub> in Nasal Congestion Observed in a Guinea Pig Model of Allergic Rhinitis

Takahashi

Tanaka

Higuchi

et al. 2012

Int Arch Allergy Immunol

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Background: Allergic rhinitis is the most common allergic disease, displaying the typical nasal symptom of congestion. Prostaglandin D₂ (PGD₂), a chemical mediator released in large amounts by mast cells upon allergic stimulation in humans, is known to be involved in nasal congestion. However, the mechanism by which this congestion occurs remains unclear. Methods: The effect of PGD₂ on the nasal airflow in guinea pigs was measured using a noninvasive approach that avoided any anesthetic effect. Isometric tension of isolated nasal mucosa and the nasal vascular corrosion resin cast technique were used to clarify the area of nasal mucosal vessels affected by PGD₂, and to examine the mechanism of PGD₂-induced nasal congestion. Moreover, the involvement of second messengers in PGD₂-induced mucosal relaxation was investigated. Results: PGD₂ induced an increase in intranasal pressure in a guinea pig model of rhinitis. Additionally, sinusoidal microvessel dilatation appeared around the septum using the vascular corrosion resin cast technique in the nasal mucosa. Moreover, relaxation of the nasal mucosa following stimulation of the prostanoid DP-1 receptor was associated with cAMP levels in the tissue. Conclusions: PGD₂-induced nasal congestion is caused by direct dilatation of the sinusoid vessels through the increase of cAMP levels in the nasal mucosa, demonstrating that the mechanism of PGD₂-induced nasal congestion is different from other chemical mediators. Consequently, antagonists for the prostanoid DP-1 receptor would be an alternative approach for the relief of nasal congestion. Alternatively, the combined administration with antagonists for other mediators involved in nasal congestion may also be a valuable therapy for allergic rhinitis.

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Modulation of Macrophage Nitric Oxide Production by Prostaglandin D2

Cited by 10 publications

References 23 publications

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

The Potential Role of Prostaglandin D<sub>2</sub> in Nasal Congestion Observed in a Guinea Pig Model of Allergic Rhinitis

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Modulation of Macrophage Nitric Oxide Production by Prostaglandin D2

Cited by 10 publications

References 23 publications

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

Niacin-induced “Flush” Involves Release of Prostaglandin D2from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model

The Potential Role of Prostaglandin D<sub>2</sub> in Nasal Congestion Observed in a Guinea Pig Model of Allergic Rhinitis

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Niacin-induced “Flush” Involves Release of Prostaglandin D₂from Mast Cells and Serotonin from Platelets: Evidence from Human Cells in Vitro and an Animal Model