Pollen-drived E1-pytoprostanes signal via PPAR-γ and NF-κB-dependent mechanisms

Stefanie Gilles, Valentina Mariani, Martina Bryce, Martin J. Mueller, Johannes Ring, Thilo Jakob, Saveria Pastore, Heidrun Behrendt, Claudia Traidl-Hoffmann

Research output: Contribution to journalArticle

Abstract

In a humid milieu such as mucosal surfaces, pollen grains do not only release allergens but also proinflammatory and immunomodulatory lipids, termed pollen-associated lipid mediators. Among these, the E1-phytoprostanes (PPE1) were identified to modulate dendritic cell (DC) function: PPE1 inhibit the DC's capacity to produce IL-12 and enhance DC mediated T H2 polarization of naive T cells. The mechanism(s) by which PPE 1 act on DC remained elusive. We thus analyzed candidate signaling elements and their role in PPE1-mediated regulation of DC function. Aqueous birch pollen extracts induced a marked cAMP response in DC that could be blocked partially by EP2 and EP4 antagonists. In contrast, PPE1 hardly induced cAMP and the inhibitory effect on IL-12 production was mostly independent of EP2 and EP4. Instead, PPE1 inhibited the LPS-induced production of IL-12 p70 by a mechanism involving the nuclear receptor PPAR-γ. Finally, PPE1 efficiently blocked NF-κB signaling in DCs by inhibiting IκB-α degradation, translocation of p65 to the nucleus, and binding to its target DNA elements. We conclude that pollen-derived PPE1 modulate DC function via PPAR-γ dependent pathways that lead to inhibition of NFκB activation and result in reduced DC IL-12 production and consecutive TH2 polarization.

Original languageEnglish
Pages (from-to)6653-6658
Number of pages6
JournalJournal of Immunology
Volume182
Issue number11
DOIs
Publication statusPublished - Jun 1 2009

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ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Gilles, S., Mariani, V., Bryce, M., Mueller, M. J., Ring, J., Jakob, T., Pastore, S., Behrendt, H., & Traidl-Hoffmann, C. (2009). Pollen-drived E1-pytoprostanes signal via PPAR-γ and NF-κB-dependent mechanisms. Journal of Immunology, 182(11), 6653-6658. https://doi.org/10.4049/jimmunol.0802613