RESUMEN
Dendritic cells (DCs), which are typical antigen-presenting cells, localize to various sites in the body, particularly the front line of infection as sentinels, and are involved in innate and adaptive immune responses. Although the functions of DCs, such as pathogen-induced cytokine production and antigen-specific T cell activation, are important for host defenses against infection and tumorigenesis, the hyper- and/or extended activation of DCs leads to inflammatory and autoimmune diseases. In the present study, ß-damascone, a major ingredient of rose fragrance, was selected from an aroma library as a candidate compound that suppresses antigen-induced immune responses. ß-Damascone inhibited the functions of DCs, including the antigen-dependent proliferation of T cells, DC-induced Th1 development, and the TLR ligand-induced production of inflammatory cytokines by DCs. The ß-damascone treatment also increased the protein level of the transcription factor NF-E2-related factor 2 (NRF2), which plays key roles in antioxidant responses, and the transcription of Hmox1 and Nqo1, target genes of NRF2, in DCs. Nrf2 -/ - DCs induced Th1-development and produced large amount of IL-12p40 even in the presence of ß-damascone, whereas these functions by Nrf2 +/- DCs were inhibited by ß-damascone under the same conditions. The intake of ß-damascone suppressed ear swelling in contact hypersensitivity (CHS) model mice, but not in CHS-induced Nrf2 -/ - mice. Collectively, the present results indicate the potential of the rose aroma compound ß-damascone, which suppresses DC-mediated immune responses by activating the NRF2 pathway in DCs, for the prevention and/or attenuation of immune-mediated diseases.
RESUMEN
ß-Damascone appeared a weak attractant close to not active to Myzus persicae, but modifications of its structure caused the avoidance of treated leaves by aphids during settling and reluctance to probe in simple choice- and no-choice experiments in previous studies. Here, the electrical penetration graph (EPG) technique, which allows monitoring of aphid probing within plant tissues, was applied to explore the biological background and localisation in plant tissues of the deterrent activities of ß-damascone and its analogues. Activity of ß-damascone and ß-damascone-derived compounds depended on their substituents, which was manifested in the variation in the potency of the behavioural effect and differences in aphid probing phases that were affected. ß-Damascone appeared a behaviourally inactive compound. The moderately active ß-damascone ester affected aphid activities only during the phloem phase. The highly active deterrents-dihydro-ß-damascol, ß-damascone acetate, δ-bromo-γ-lactone, and unsaturated γ-lactone-affected pre-phloem and phloem aphid probing activities. The most effective structural modification that evoked the strongest negative response from M. persicae was the transformation of ß-damascone into δ-bromo-γ-lactone. The behavioural effect of this transformation was demonstrated in frequent interruption of probing in peripheral tissues, which caused repeated failures in finding sieve elements, and reduction in the ingestion time during the phloem phase in favour of watery salivation. The inhibition of aphid probing at both the pre-phloem and phloem levels reveals the passage of the compounds studied through the plant surface and their distribution within plant tissues in a systemic way, which may reduce the risk of the transmission of non-persistent and persistent viruses.