Prostaglandin E2 inhibits migration of colonic lamina propria fibroblasts

Rieder, Florian; Georgieva, M; Schirbel, Anja; Artinger, Monika; Zügner, Anita; Blank, Martin; Brenmoehl, Julia; Schölmerich, Jürgen; Rogler, Gerhard

doi:10.1002/ibd.21255

Cited by 35 publications

(40 citation statements)

References 42 publications

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“…Thus, the decrease in muscle migration by PPARc is most probably due to an increase in intracellular cAMP facilitated by PGE 2 . This is consistent with observations with other agents, such as bagonists, that increase intracellular cAMP and decrease airway [21] and vascular [22] smooth muscle cell and fibroblast migration [23]. It is likely that cAMP modulates the morphology of smooth muscle cells by inhibiting a Rac-dependent signalling pathway resulting in disassembly of actin stress fibres and lamellipodia, loss of focal adhesions and the formation of small F-actin rings [24], thus decreasing the ability of cells to migrate.…”

Section: Discussionsupporting

confidence: 77%

PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis

et al. 2012

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Airway smooth muscle cells produce extracellular matrix proteins, which in turn can promote smooth muscle survival, proliferation and migration. Currently available therapies have little effect on airway smooth muscle matrix production and migration. Peroxisome proliferatoractivated receptor (PPAR) ligands are reported to decrease migration and matrix production in various cell lines. In this study, we examined the effect of PPAR ligands on human airway smooth muscle (HASM) matrix production and migration.PPAR expression was examined by RT-PCR and Western blotting. Endogenous PPAR activity was examined by transfecting cells with a PPAR response element-luciferase reporter plasmid.We observed that HASM cells express PPARa, b and c. A six-fold induction of luciferase activity was observed by stimulating cells with a pan-agonist, indicating endogenous PPAR activity. The PPAR ligands ciglitazone, 15-deoxy-D12,14-prostaglandin J 2 and WY-14643 decreased migration towards platelet-derived growth factor receptor. This was not mediated by inhibiting Akt phosphorylation or promoting PTEN activity, but partly through cyclooxygenase-2 induction and prostaglandin E 2 production that increased cyclic AMP levels in the cells. All three ligands also caused an inhibition of collagen and fibronectin secretion by cultured smooth muscle cells.We conclude that PPAR ligands decrease HASM migration and matrix production and are, therefore, potentially useful for modulating airway remodelling.

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Section: Discussionsupporting

confidence: 77%

PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis

et al. 2012

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“…Studies on EP4 receptor knockout mice also suggested a protective role for PGE 2 against inflammation (Kabashima et al, 2002). On the other hand, PGE 2 may lead to impaired mucosal healing or excessive fibrosis by inhibiting the migration of the colonic lamia propria fibroblasts from patients with Crohn's disease (Rieder et al, 2010). PGE 2 production is increased in IBD (Baumeister et al, 1996), and it has been suggested as a mediator and/or prognostic marker in IBD (Wierciń ska-Drapalo et al, 1999;Sheibanie et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Hemokinin-1 Stimulates Prostaglandin E₂ Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase

Dai

Perera²,

King³

et al. 2011

J Pharmacol Exp Ther

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Hemokinin-1 (HK-1) is a newly identified tachykinin, originating from the immune system rather than neurons, and may participate in the immune and inflammatory response. In colonic mucosa of patients with inflammatory bowel disease (IBD), up-regulation of the TAC4 gene encoding HK-1 and increased production of prostaglandin E 2 (PGE 2 ) occur. Our aim was to examine the mechanistic link between human HK-1 and PGE 2 production in normal human colon. Exogenous HK-1 (0.1 M) for 4 h evoked an increased PGE 2 release from colonic mucosal and muscle explants by 10-and 3.5-fold, respectively, compared with unstimulated time controls. The HK-1-stimulated PGE 2 release was inhibited by the tachykinin receptor antagonists (and was also inhibited by the cyclooxygenase (COX)-2 inhibitor N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide) (NS-398)but not by the COX-1 inhibitor 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole (SC-560). A parallel study with substance P showed similar results. Molecular studies with HK-1-treated explants demonstrated a stimulatory effect on COX-2 expression at both transcription and protein levels. It is noteworthy that this was coupled with HK-1-induced down-regulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA and protein expression. Immunoreactivity for 15-PGDH occurred on inflammatory cells, epithelial cells, platelets, and ganglia. This finding provides an additional mechanism for HK-1-evoked PGE 2 increase, in which HK-1 may interfere with the downstream metabolism of PGE 2 by suppressing 15-PGDH expression. In conclusion, our results uncover a novel inflammatory role for HK-1, which signals via NK 1 and NK 2 receptors to regulate PGE 2 release from human colonic tissue, and may further explain a pathological role for HK-1 in IBD when abnormal levels of PGE 2 occur.

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“…It has been suggested that a combination of ASCA, P-ANCA and anti-OmpC or a panel of antiglycan antibodies may aid in differentiation of CD from UC. In addition, the use of a panel of anticarbohydrate antibodies may provide additional help in distinguishing IBD from non-IBD disease patterns [27,35,47,48]. However, it should be noted that the presence of ASCA and P-ANCA does not mean the confirmation of the IBD diagnosis.…”

Section: The Role Of Serologic Markers In Ibd Diagnosismentioning

confidence: 99%

“…Antiglycan antibodies are useful in differentiation between CD and UC: patients with CD who are positive for at least one of the above-mentioned antiglycan antibodies could be differentiated from UC with approximately 80% sensitivity and more than 90% specificity [7,34,35,36]. …”

Section: Recently Characterized Serologic Ibd Markersmentioning

confidence: 99%

The Role of Autoantibodies in Inflammatory Bowel Disease

Herszényi

Tulassay

2012

Dig Dis

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The search for the underlying trigger of an inappropriate inflammatory reaction characteristic of inflammatory bowel diseases (IBD) has led to the discovery of several antibodies. The panel of serologic markers for IBD is rapidly expanding. Serologic markers hold the promise of helping researchers and clinicians to better understand IBD heterogeneity and natural history. The real importance of the antibodies produced against various microbial and autoantigens is still uncertain. Whether these antibodies play a primary role in the pathogenesis of IBD, or their presence is only a consequence of the inflamed mucosa is a fundamental question that remains to be clarified. The impact of the routine evaluation of these serologic markers in the everyday clinical IBD diagnostic algorithm is questionable due to their limited sensitivity. Despite their great potential, the routine use of serologic markers for diagnosis and follow-up is currently not justified. However, their correlation with disease phenotype and behavior is more established. A combination of serum markers has been shown to be of more value compared to using single markers alone. The ongoing challenge is how to best utilize these serologic markers to provide clinically relevant information in a cost-effective manner. Further prospective clinical trials are needed to determine their exact role in pathogenesis and practical clinical importance. We review the current standpoint of the clinical impact of various established and newly suggested markers in Crohn’s disease and ulcerative colitis.

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Prostaglandin E2 inhibits migration of colonic lamina propria fibroblasts

Cited by 35 publications

References 42 publications

PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis

PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis

Hemokinin-1 Stimulates Prostaglandin E₂ Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase

The Role of Autoantibodies in Inflammatory Bowel Disease

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Prostaglandin E2 inhibits migration of colonic lamina propria fibroblasts

Cited by 35 publications

References 42 publications

PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis

PPAR ligands decrease human airway smooth muscle cell migration and extracellular matrix synthesis

Hemokinin-1 Stimulates Prostaglandin E2 Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase

The Role of Autoantibodies in Inflammatory Bowel Disease

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Hemokinin-1 Stimulates Prostaglandin E₂ Production in Human Colon through Activation of Cyclooxygenase-2 and Inhibition of 15-Hydroxyprostaglandin Dehydrogenase