Role of prostaglandin D<sub>2</sub> and E<sub>2</sub> terminal synthases in chronic rhinosinusitis

Okano, Mitsuhiro; Fujiwara, Tazuko; Yamamoto, Miki; Sugata, Yuji; Matsumoto, Rie; Fukushima, K.; Yoshino, Tadashi; Shimizu, Koïchi; Eguchi, Naomi; Kiniwa, Mamoru; Urade, Yoshihiro; Nishizaki, Kazunori

doi:10.1111/j.1365-2222.2006.02528.x

Cited by 59 publications

(54 citation statements)

References 48 publications

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“…Thus, PGE 2 may not play a primary role in NK cell dysfunction in CRS patients, compatible with the inverse correlation between PGE 2 levels and eosinophilic inflammation in CRS patients 17,44 . In summary, we here show a previously unappreciated aspect of a proinflammatory effect of PGD 2 on the pathophysiology of CRS in the context of NK cell dysfunction.…”

Section: Discussionmentioning

confidence: 61%

“…In comparison, the levels of PGE 2 and its metabolites were slightly elevated but not significantly different in the CRS group. Thus, PGD 2 may be a potential candidate mediator implicated in NK cell dysfunction in CRS, compatible with an elevated expression of PGDS and production of PGD 2 in CRS 17,18 . PGD 2 attenuates NK cell effector functions.…”

Section: Nk Cells Regulate Eosinophilic Inflammation In a Murine Modementioning

confidence: 84%

“…PGD 2 functions through two receptors, DP1 and DP2 and is important for Th2-mediated inflammatory disease via the recruitment of Th2 cells, eosinophils, and basophils. In an allergic asthma mouse model, PGD 2 and PGDS have been implicated in triggering an allergic response, such as eosinophilia, airway hyperreactivity, mucus production, and increased abundance of Th2 cytokines 16,17 . In CRSwNP patients, the levels of PGDS mRNA expression in inflamed sinus mucosa were elevated, independently of atopic status.…”

Section: Discussionmentioning

confidence: 99%

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Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Kim

Jang

2015

Journal of Allergy and Clinical Immunology

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Eosinophils play a major pathologic role in the pathogenesis of diverse inflammatory diseases including chronic rhinosinusitis (CRS). Dysregulated production of prostaglandin (PG), particularly PGD 2 , is considered to be an important contributing factor to eosinophilic inflammation in CRS primarily through proinflammatory and chemotactic effects on eosinophils. Here, we provide evidence that PGD 2 can promote eosinophilic inflammation through a suppression of Natural killer (NK) cell effector function and NK cell-mediated eosinophil regulation. Eosinophil apoptosis mediated by NK cells was significantly decreased in CRS patients compared with healthy controls. This decrease was associated with NK cell dysfunction and eosinophilic inflammation. Tissue eosinophils were positively correlated with blood eosinophils in CRS patients. In a murine model of CRS, NK cell depletion caused an exacerbation of blood eosinophilia and eosinophilic inflammation in the sinonasal tissue. PGD 2 and its metabolite, but not PGE 2 and a panel of cytokines including TGF-β, were increased in CRS patients compared with controls. Effector functions of NK cells were potently suppressed by PGD 2 -dependent, rather than PGE 2 -dependent, pathway in controls and CRS patients. Thus, our results suggest decreased NK cell-mediated eosinophil regulation, possibly through an increased level of PGD 2 , as a previously unrecognized link between PG dysregulation and eosinophilic inflammation in CRS.

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Section: Discussionmentioning

confidence: 61%

Section: Nk Cells Regulate Eosinophilic Inflammation In a Murine Modementioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Kim

Jang

2015

Journal of Allergy and Clinical Immunology

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“…Therefore, it is not surprising that studies have shown the PGD 2 signaling pathway plays a role in allergic rhinitis, asthma [31,32] atopic dermatitis [33,34] CRS and nasal polyposis [35][36][37], and aspirin exacerbated respiratory disease (AERD) [38]. PGD 2 has also been found to be a more potent bronchoconstrictor than histamine in normal and atopic individuals [39].…”

Section: Prostaglandin D 2 (Pgd 2 )mentioning

confidence: 99%

Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells

MR¹,

TA²

2016

Immunome Res

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ILC2s were originally found to be activated by epithelial cell derived cytokines to induce the secretion of Th2 cytokines, IL-5 and IL-13. Recent research has shown that lipid mediators play a large role in the activation and inhibition of ILC2 function. Unlike the traditional epithelial cell derived cytokines IL-33 and IL-25, lipid mediators have been shown to promote ILC2 secretion of not only IL-5 and IL-13, but the secretion of IL-4 as well. Prostaglandin D 2 has been shown to be a potent chemoattractant of ILC2s as well as a potent activator of ILC2s to release Th2 cytokines. In addition to prostaglandin D 2 , cysteinyl leukotrienes also activate ILC2s to secrete Th2 cytokines during inflammation. Notably, lipid mediators have been shown to work in concert with epithelial cell derived cytokines to increase IL-5 and IL-13 secretion from ILC2s. On the other hand, lipid meditators prostaglandin I 2 and lipoxin A 4 are the first identified lipid mediator inhibitors of ILC2 function, and thus limit ILC2 contribution to Th2 inflammation. ILC2s play a potential significant role in Th2 mediated inflammation in a variety of allergic disease states, such as asthma, atopic dermatitis, and chronic rhinosinusitis. The identification of lipid mediators as activators and inhibitors of ILC2 function provides additional therapeutic targets for altering ILC2 function during disease states.

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“…Given that eosinophil expression greatly exceeds that of mast cells in AERD it is reasonable to speculate that eosinophils maybe also be an important source of PGD 2 . Expression of hPGDS has been observed in NP of CRS patients 18 and one report suggested that a subpopulation of eosinophils in the NP were one source of the enzyme 19 .…”

Section: Introductionmentioning

confidence: 99%

Eosinophil Production of PGD2 in Aspirin-Exacerbated Respiratory Disease

Steinke

Negri

Baker

et al. 2016

Journal of Allergy and Clinical Immunology

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Background-Aspirin-exacerbated respiratory disease (AERD) differs from aspirin tolerant disease due in part to eosinophilic tissue infiltration and over-expression of arachidonic acid metabolic pathway components that lead to enhanced secretion of cysteinyl leukotrienes (CysLT) and prostaglandin D 2 (PGD 2 ) observed constitutively and, paradoxically, in response to aspirin and other cyclooxygenase inhibitors. We have previously demonstrated the capacity of interferon (IFN)-γ to drive CysLT expression and response.

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Role of prostaglandin D₂ and E₂ terminal synthases in chronic rhinosinusitis

Abstract: These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation.

Cited by 59 publications

References 48 publications

Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells

Eosinophil Production of PGD2 in Aspirin-Exacerbated Respiratory Disease

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Role of prostaglandin D2 and E2 terminal synthases in chronic rhinosinusitis

Abstract: These results suggest that PGDS and PGES display an opposite and important role in the pathophysiology of CRS such as polyp formation, and more specifically, a biased expression of these synthases might contribute to the development of CRS by affecting eosinophilic inflammation.

Cited by 59 publications

References 48 publications

Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Natural Killer Cells Regulate Eosinophilic Inflammation in Chronic Rhinosinusitis

Lipid Mediator Regulation of Group 2 Innate Lymphoid Cells

Eosinophil Production of PGD2 in Aspirin-Exacerbated Respiratory Disease

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Product

Resources

About

Role of prostaglandin D₂ and E₂ terminal synthases in chronic rhinosinusitis