Role of C3a as a Novel Regulator of 25(OH)D3 to 1α,25-Dihydroxyvitamin D3 Metabolism in Upper Airway Epithelial Cells.

In patients with chronic rhinosinusitis with nasal polyps, primary human sinonasal epithelial cell (HSNEC) 1α-hydroxylase levels are reduced, as is their ability to metabolize 25-hydroxycholecalciferol [25(OH)D3] to its active metabolite, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3]. In this study, we sought to identify the factor responsible for the regulation of HSNEC metabolism of 25(OH)D3, focusing on C3 and C3a. Multiple inhaled irritants trigger the release of complement components, C3 and C3a, leading to suppression of 1α-hydroxylase levels in HSNECs. Recombinant C3a was able to decrease 1α-hydroxylase and impair 25(OH)D3 to 1,25(OH)2D3 metabolism, while addition of a C3a receptor antagonist restored conversion. Conversely, 1,25(OH)2D3 suppressed Aspergillus fumigatus-induced C3 and C3a levels in HSNEC supernatant. Given the ability of 1,25(OH)2D3 to modulate LL37 in other cell types, we examined its regulation in HSNECs and relationship to C3a. 1,25(OH)2D3 stimulated the secretion of LL37, whereas A. fumigatus and C3a suppressed it. Conversely, LL37 reduced the release of C3/C3a by HSNECs. Lastly, oral steroid use and in vitro dexamethasone application both failed to increase 1α-hydroxylase or reduce C3a levels. In summary, in this article, we describe for the first time a novel relationship between complement activation and local vitamin D metabolism in airway epithelial cells. The presence of elevated C3/C3a in patients with asthma and/or chronic rhinosinusitis with nasal polyps may account for their impaired HSNEC 25(OH)D3 to 1,25(OH)2D3 metabolism and explain why they receive limited therapeutic benefit from oral vitamin D3 supplementation.

Ultrasound treatments improve the microbiological quality of water reservoirs used for the irrigation of fresh produce.

Irrigation water has been highlighted as a source of microbial contamination in produce. Water treatment has been recommended as an intervention strategy to reduce microbial risks associated to irrigation water. Commercial water treatments mostly depend on chemical agents; although growers search for greener alternatives to chemical biocides. Ultrasounds (US) have been proposed as an environmentally friendly technology for irrigation water. In the present study, the suitability of two US treatments (20kHz: US20 and 40kHz: US40 at a specific energy (Es) of 745J/L) and one chlorine treatment (1-2ppm free chlorine) was evaluated and compared to the untreated control. Five water reservoirs belonging to five commercial intensive farms were selected as representative of irrigation practices generally used in south of Europe. All tested water treatments were able to reduce microbial loads, including Escherichia coli (0.5-0.6 log units), to values that were accepted in most of the recommended guidelines of good agricultural practices (≤2logunits). The obtained reductions were lower than those previously reported for these water treatment technologies in lab-scale tests. High microbial reductions are commonly obtained in laboratory studies, yielding impressive results. However, when the same treatments are applied under real commercial conditions, microbial reductions are usually less impressive. All water treatments were able to reduce COD of irrigation water when compared to the untreated control. COD reductions obtained using chlorine (≥430mg/L) and US 20 (~100mg/L) were higher than those observed using US 40 (<50mg/L). The impact of the water quality on the efficacy of US treatments was evaluated in two types of water including surface water and treated wastewater. It was found that the quality of the irrigation water significantly influences the efficacy of the ultrasound treatment. Correlations between indicator parameters have been also evaluated. Obtained results showed that high algae counts were well correlated with high levels of coliforms and E. coli. It could be concluded that US can be proposed as an alternative water treatment to chemical treatments to preserve microbial quality of irrigation water stored in water reservoirs reducing the environmental impact.