Functional Prostaglandin-Endoperoxide Synthase 2 Polymorphism Predicts Poor Outcome in Sarcoidosis

Hill, Michael; Papafili, Anastasia; Booth, Helen; Lawson, Phillippa J.; Hubner, Marianne; Beynon, Huw; Read, Catherine; Lindahl, Gisela; Marshall, Richard P.; McAnulty, Robin J.; Laurent, Geoffrey J.

doi:10.1164/rccm.200512-1839oc

Cited by 54 publications

(39 citation statements)

References 43 publications

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“…This defect may, in part, involve the presence of gene polymorphisms. In support of this hypothesis, a functional promoter polymorphism in the COX-2 gene (PTGS2) which reduces gene expression [24] has recently been associated with susceptibility to sarcoidosis [25]. Moreover, the association appears to be driven by those patients with persistent progressive disease who are most likely to develop pulmonary fibrosis [25].…”

Section: Cytokines and Lipid Mediators As Inhibitors Of Fibroblast Fumentioning

confidence: 97%

Regulation of matrix turnover: fibroblasts, forces, factors and fibrosis

Laurent

Chambers

Hill

et al. 2007

Biochemical Society Transactions

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Fibroblasts are multifunctional cells that are responsible for matrix homoeostasis, continuously synthesizing and degrading a diverse group of extracellular molecules and their receptors. Rates of turnover of matrix molecules and the proteases that degrade them are normally under the control of diverse chemical and mechanical cues, with cytokines, growth factors, proteases, lipid mediators and mechanical forces playing roles. The maintenance of this homoeostasis is vital to the preservation of normal tissue function and is clearly lost in chronic diseases of the joints, skin and internal organs where destruction and excessive deposition is seen. Current research is focusing on defining the key pathways of activation either in resident fibroblasts, matrix-producing cells derived from circulating fibrocytes, or from transdifferentiation of resident cells. The common downstream signalling pathways are also being defined, as well as the gene interactions leading to altered cell phenotype. The present article reviews these findings and our current concepts of the key molecular events leading to tissue damage and excessive matrix deposition in tissue fibrosis. These studies are leading to an appreciation of the complexity of events with multiple pathways involved, but, as the facts emerge, we are finding promising new ways to treat fibrosis and halt the inexorable progression that is a feature of so many fibrotic and remodelling disorders.

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Section: Cytokines and Lipid Mediators As Inhibitors Of Fibroblast Fumentioning

confidence: 97%

Regulation of matrix turnover: fibroblasts, forces, factors and fibrosis

Laurent

Chambers

Hill

et al. 2007

Biochemical Society Transactions

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“…Interesting results are also delivered by studies on non-HLA polymorphisms. For instance, -765G>C promoter polymorphism in prostaglandin-endoperoxide synthase 2 gene, encoding a key regulatory enzyme in the synthesis of anifibrotic prostaglandin E2, may identify patients at increased risk of lung fibrosis (Hill et al, 2006). Other data suggest that the haplotype containing the -509C and codon 10T in the TGF-β1 gene predispose to more severe sarcoidosis, whereas -509T and codon 10C are protective (Jonth et al, 2007).…”

Section: Geneticsmentioning

confidence: 99%

Prognostic Factors in Sarcoidosis

Piotrowski¹

2011

Sarcoidosis Diagnosis and Management

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“…Die Vari− ante ist sowohl mit der Empfänglichkeit als auch mit einem un− günstigen Verlauf der Sarkoidose vergesellschaftet [91]. Das natural resistance−associated macrophage proteine−1 (NRAMP−1 [in neuer Nomenklatur: SLC11A1]) findet sich in Ma− krophagen und Polymorphkernigen, wo es eine wichtige Rolle bei der Aktivierung übernimmt.…”

Section: Andere Kandidatengeneunclassified