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 TH2 polarization of naive T cells. The mechanism(s) by which PPE1 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.
Pollen allergy is characterized by a T H 2-biased immune response to pollen-derived allergens. However, pollen-exposed epithelia do not encounter pure allergen but rather a plethora of protein and non-protein substances. We demonstrated that pollen liberate lipids with chemical and functional similarities to leukotriens and prostaglandins -the pollen associated lipid mediators (PALMs). To date, two main groups of PALMs have been characterized: The immunostimulatory PALMs activating innate immune cells such as neutrophils and eosinophils, and the immunomodulatory E 1 -phytoprostanes blocking IL-12 production of dendritic cells, resulting in the preferential induction of T H 2 responses. This article reviews our work in the field of PALMs and their effects on cells of the innate and adoptive immune system. From recent results a general picture starts to emerge in which PALMs (and possibly other pollen-associated substances) mayindependently from protein allergens -propagate an overall T H 2 favoring micromilieu in pollen exposed tissue of predisposed individuals.
Background: Epidemiologic studies reveal a dramatic increase in allergies in the last decades. Air pollution is considered to be one of the factors responsible for this augmentation. The aim of this study was to analyze the impact of urbanization on birch pollen. The birch pollen proteome was investigated in order to identify differences in protein abundance between pollen from rural and urban areas. The allergenicity of birch pollen from both areas was evaluated by assessing its chemotactic potency as well as its protein and allergen contents. Methods: Difference gel electrophoresis (DIGE) was used to analyze the pollen proteome. The chemotactic activity of aqueous pollen extracts was determined by migration assays of human neutrophils. Results: DIGE revealed 26 differences in protein spot intensity between pollen from urban and rural areas. One of these proteins was identified by de novo sequencing as the 14-3-3 protein, which resembles a stress-induced factor in other plant species. Furthermore, extracts from pollen collected in urban areas had higher chemotactic activity on human neutrophils compared to pollen from rural sites. Conclusions: The present study points to an impact of air pollution on allergen carrier proteome and release of chemotactic substances. The increment in proinflammatory substances such as pollen-associated lipid mediators might contribute to the described urban-rural gradient of allergy prevalence. Furthermore, our study suggests that allergenicity is determined by more than the sole allergen content.
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