PuSH - Publikationsserver des Helmholtz Zentrums München: Pollen-derived E1-phytoprostanes signal via PPAR-γ and NF-κB-dependent mechanisms.

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Gilles, S. ; Mariani, V.* ; Bryce, M. ; Mueller, M.J.* ; Ring, J.* ; Jakob, T.* ; Pastore, S.* ; Behrendt, H. ; Traidl-Hoffmann, C.

Pollen-derived E1-phytoprostanes signal via PPAR-γ and NF-κB-dependent mechanisms.

J. Immunol. 182, 6653-6658 (2009)

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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 E(1)-phytoprostanes (PPE(1)) were identified to modulate dendritic cell (DC) function: PPE(1) inhibit the DC's capacity to produce IL-12 and enhance DC mediated T(H)2 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 PPE(1)-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, PPE(1) hardly induced cAMP and the inhibitory effect on IL-12 production was mostly independent of EP2 and EP4. Instead, PPE(1) inhibited the LPS-induced production of IL-12 p70 by a mechanism involving the nuclear receptor PPAR-gamma. Finally, PPE(1) efficiently blocked NF-kappaB signaling in DCs by inhibiting IkappaB-alpha degradation, translocation of p65 to the nucleus, and binding to its target DNA elements. We conclude that pollen-derived PPE(1) modulate DC function via PPAR-gamma dependent pathways that lead to inhibition of NFkappaB activation and result in reduced DC IL-12 production and consecutive T(H)2 polarization.

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