PGD Synthase and PGD<b><sub>2</sub></b>in Immune Resposne

Joo, Myungsoo; Sadikot, Ruxana T.

doi:10.1155/2012/503128

Cited by 92 publications

(82 citation statements)

References 63 publications

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“…However, the immunostimulatory mechanisms of these lipid mediators are not well defined (45). Since 15d-PGJ 2 is a PPAR␥ ligand, we investigated whether these effects were mediated by PPAR␥ and whether PPAR␥ agonists enhance bacterial phagocytosis and killing.…”

Section: Ppar␥ Agonists Enhanced Phagocytosis and Bacterial Clearancementioning

confidence: 99%

Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma

et al. 2016

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fThe pathogenic profile of Pseudomonas aeruginosa is related to its ability to secrete a variety of virulence factors. Quorum sensing (QS) is a mechanism wherein small diffusible molecules, specifically acyl-homoserine lactones, are produced by P. aeruginosa to promote virulence. We show here that macrophage clearance of P. aeruginosa (PAO1) is enhanced by activation of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPAR␥). Macrophages treated with a PPAR␥ agonist (pioglitazone) showed enhanced phagocytosis and bacterial killing of PAO1. It is known that PAO1 QS molecules are inactivated by PON-2. QS molecules are also known to inhibit activation of PPAR␥ by competitively binding PPAR␥ receptors. In accord with this observation, we found that infection of macrophages with PAO1 inhibited expression of PPAR␥ and PON-2. Mechanistically, we show that PPAR␥ induces macrophage paraoxonase 2 (PON-2), an enzyme that degrades QS molecules produced by P. aeruginosa. Gene silencing studies confirmed that enhanced clearance of PAO1 in macrophages by PPAR␥ is PON-2 dependent. Further, we show that PPAR␥ agonists also enhance clearance of P. aeruginosa from lungs of mice infected with PAO1. Together, these data demonstrate that P. aeruginosa impairs the ability of host cells to mount an immune response by inhibiting PPAR␥ through secretion of QS molecules. These studies define a novel mechanism by which PPAR␥ contributes to the host immunoprotective effects during bacterial infection and suggest a role for PPAR␥ immunotherapy for P. aeruginosa infections.

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Section: Ppar␥ Agonists Enhanced Phagocytosis and Bacterial Clearancementioning

confidence: 99%

Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma

et al. 2016

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“…We and others have shown that activation of cyclooxygenase-2 (COX-2) and production of lipid mediators play a pivotal immunomodulatory role in fungal, viral, and bacterial infections (21)(22)(23)(24)(25). In particular, PGE 2 has immunosuppressive effects and impairs bacterial clearance (22,23,(26)(27)(28)(29), whereas PGD 2 has been shown to have immunostimulatory effects (30,31).…”

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confidence: 99%

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Yuan

Panchal

Syed

et al. 2013

The Journal of Immunology

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Stomatococcus mucilaginosus is an oral commensal that has been occasionally reported to cause severe infections in immunocompromised patients. There is no information about the pathogenic role of S. mucilaginosus in airway infections. In a cohort of 182 subjects with bronchiectasis, we found that 9% were colonized with S. mucilaginosus in their lower airways by culture growth from bronchoalveolar lavage. To address the pathogenic potential of S.mucilaginosus, we developed a murine model of S. mucilaginosus lung infection. Intratracheal injection of S. mucilaginosus in C57BL/6 mice resulted in a neutrophilic influx with production of proinflammatory cytokines, chemokines, and lipid mediators, mainly PGE2 with induction of cyclooxygenase-2 (COX-2) in the lungs. Presence of TLR2 was necessary for induction of COX-2 and production of PGE2 by S. mucilaginosus. TLR2-deficient mice showed an enhanced clearance of S. mucilaginosus compared with wild-type mice. Administration of PGE2 to TLR2−/− mice resulted in impaired clearance of S. mucilaginosus, suggesting a key role for COX-2–induced PGE2 production in immune response to S. mucilaginosus. Mechanistically, induction of COX-2 in macrophages was dependent on the p38-ERK/MAPK signaling pathway. Furthermore, mice treated with S. mucilaginosus and Pseudomonas aeruginosa showed an increased mortality compared with mice treated with PA103 or S. mucilaginosus alone. Inhibition of COX-2 significantly improved survival in mice infected with PA103 and S. mucilaginosus. These data provide novel insights into the bacteriology and personalized microbiome in patients with bronchiectasis and suggest a pathogenic role for S. mucilaginosus in patients with bronchiectasis.

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“…Several subtypes of PGs with distinct activities have been described, including PGE 2 , PGI 2, and PGD 2 (Harris et al, 2002). Among them, PGD 2 has been characterized as eosinophil chemo attractant (Monneret et al, 2001) and anti-inflammatory agent (Joo et al, 2007;Joo and Sadikot, 2012;Murata et al, 2013). Intratracheal administration of PGD 2 has been shown to decrease the bacterial load in the lungs of Pseudomonas aeruginosa-infected mice (Joo et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

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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PGD Synthase and PGD₂in Immune Resposne

Cited by 92 publications

References 63 publications

Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma

Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

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PGD Synthase and PGD2in Immune Resposne

Cited by 92 publications

References 63 publications

Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma

Enhanced Clearance of Pseudomonas aeruginosa by Peroxisome Proliferator-Activated Receptor Gamma

Induction of Cyclooxygenase-2 Signaling by Stomatococcus mucilaginosus Highlights the Pathogenic Potential of an Oral Commensal

Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions

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PGD Synthase and PGD₂in Immune Resposne