Dataset Information

Prostaglandin E₂ suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells.

ABSTRACT:

Background

Endogenous prostanoids have been suggested to modulate sensitization during experimental allergic asthma, but the specific role of prostaglandin (PG) E₂ or of specific E prostanoid (EP) receptors is not known.

Objective

Here we tested the role of EP2 signaling in allergic asthma.

Methods

Wild-type (WT) and EP2(-/-) mice were subjected to ovalbumin sensitization and acute airway challenge. The PGE2 analog misoprostol was administered during sensitization in both genotypes. In vitro culture of splenocytes and flow-sorted dendritic cells and T cells defined the mechanism by which EP2 exerted its protective effect. Adoptive transfer of WT and EP2(-/-) CD4 T cells was used to validate the importance of EP2 expression on T cells.

Results

Compared with WT mice, EP2(-/-) mice had exaggerated airway inflammation in this model. Splenocytes and lung lymph node cells from sensitized EP2(-/-) mice produced more IL-13 than did WT cells, suggesting increased sensitization. In WT but not EP2(-/-) mice, subcutaneous administration of misoprostol during sensitization inhibited allergic inflammation. PGE₂ decreased cytokine production and inhibited signal transducer and activator of transcription 6 phosphorylation by CD3/CD28-stimulated CD4(+) T cells. Coculture of flow cytometry-sorted splenic CD4(+) T cells and CD11c(+) dendritic cells from WT or EP2(-/-) mice suggested that the increased IL-13 production in EP2(-/-) mice was due to the lack of EP2 specifically on T cells. Adoptive transfer of CD4(+) EP2(-/-) T cells caused greater cytokine production in the lungs of WT mice than did transfer of WT CD4(+) T cells.

Conclusion

We conclude that the PGE2-EP2 axis is an important endogenous brake on allergic airway inflammation and primarily targets T cells and that its agonism represents a potential novel therapeutic approach to asthma.

SUBMITTER: Zaslona Z

PROVIDER: S-EPMC3960315 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

Prostaglandin E₂ suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells.

Zasłona Zbigniew Z Okunishi Katsuhide K Bourdonnay Emilie E Domingo-Gonzalez Racquel R Moore Bethany B BB Lukacs Nicholas W NW Aronoff David M DM Peters-Golden Marc M

The Journal of allergy and clinical immunology 20130924 2

<h4>Background</h4>Endogenous prostanoids have been suggested to modulate sensitization during experimental allergic asthma, but the specific role of prostaglandin (PG) E₂ or of specific E prostanoid (EP) receptors is not known.<h4>Objective</h4>Here we tested the role of EP2 signaling in allergic asthma.<h4>Methods</h4>Wild-type (WT) and EP2(-/-) mice were subjected to ovalbumin sensitization and acute airway challenge. The PGE2 analog misoprostol was administered during sensitization in both g ...[more]

PMID: 24075232

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Project description:BackgroundAllergic conjunctivitis (AC) is an inflammation caused by a hypersensitive immune reaction of conjunctiva to external allergens. The microRNA (miRNA) miR-146a has been reported to suppress the exacerbation of inflammation. However, the underlying influence and mechanism of miR-146a in AC has not been completely elucidated.MethodsWe first successfully established an AC mouse model and AC cell model. After each model was treated based on the experimental purposes, miR-146a, FOXP3, and homeodomain-interacting protein kinases 3 (HIPK3) expressions were estimated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The levels of immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) were assessed using enzyme-linked immunosorbent assay (ELISA) kits; the related proteins were analyzed by western blot, immunofluorescence, or immunohistochemistry (IHC) assays; the interaction between miR-146a and HIPK3 were validated by a dual-luciferase reporter gene assay; and the inflammatory infiltration was certified by hematoxylin and eosin (H&E) staining.ResultsOur results indicated that miR-146a and FOXP3 were downregulated in AC model mice. Meanwhile, miR-146a overexpression could upregulate FOXP3 and inhibit inflammatory response in TGF-β-induced thymocytes. Besides, our results testified that HIPK3, as a target gene of miR-146a, could reverse miR-146a-mediated FOXP3 upregulation and inflammation inhibition. Moreover, we discovered that miR-146a could downregulate p-STAT3 by targeting HIPK3, and activation of STAT3 also could reverse miR-146a-mediated inflammation suppression in TGF-β-induced thymocytes. More importantly, miR-146a could ameliorate inflammatory infiltration and downregulate HIPK3 and p-STAT3 in AC model mice.ConclusionsWe demonstrated a possible protective mechanism by the miR-146a/HIPK3/STAT3 axis, by which decrease of miR-146a could aggravate the inflammation of AC.

Dataset Information

Prostaglandin E₂ suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells.

Background

Objective

Methods

Results

Conclusion

Publications

Prostaglandin E₂ suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells.

Similar Datasets

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