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We investigated the effects of resolvin E (RvE) 1, RvE2, and RvE3 on IL‐4‐ and IL‐33‐stimulated bone marrow‐derived dendritic cells (BMDCs) from house dust mite (HDM)‐sensitized mice. We also investigated the role of RvE3 in a murine model of HDM‐induced airway inflammation. In vitro, BMDCs from HDM‐sensitized mice were stimulated with IL‐4 and IL‐33 and then treated with RvE1, RvE2, RvE3, or vehicle. RvE1, RvE2, and RvE3 suppressed IL‐23 release from BMDCs. In vivo, RvE3 administrated to HDM‐sensitized and challenged mice in the resolution phase promoted a decline in total numbers of inflammatory cells and eosinophils, reduced levels of IL‐23 and IL‐17 in lavage fluid, and suppressed IL‐23 and IL‐17A mRNA expression in lung and peribronchial lymph nodes. RvE3 also reduced resistance in the lungs of HDM‐sensitized mice. A NanoBiT β‐arrestin recruitment assay using human embryonic kidney 293 cells revealed that pretreatment with RvE3 suppressed the leukotriene B4 (LTB4)‐induced β‐arrestin 2 binding to LTB4 receptor 1 (BLT1R), indicating that RvE3 antagonistically interacts with BLT1R. Collectively, these findings indicate that RvE3 facilitates the resolution of allergic airway inflammation, partly by regulating BLT1R activity and selective cytokine release by dendritic cells. Our results accordingly identify RvE3 as a potential therapeutic target for the management of asthma.—Sato, M., Aoki‐Saito, H., Fukuda, H., Ikeda, H., Koga, Y., Yatomi, M., Tsurumaki, H., Maeno, T., Saito, T., Nakakura, T., Mori, T., Yanagawa, M., Abe, M., Sako, Y., Dobashi, K., Ishizuka, T., Yamada, M., Shuto, S., Hisada, T. Resolvin E3 attenuates allergic airway inflammation via the interleukin‐23‐interleukin‐17A pathway. FASEB J. 33, 12750–12759 (2019). http://www.fasebj.org

The effects of bethanechol and atropine on the release of acetylcholine (ACh) from bullfrog sympathetic preganglionic nerve terminals were examined electrophysiologically. Bethanechol (1 mm) caused no depolarization of sympathetic preganglionic nerve terminals, whereas carbachol or ACh in the same concentration induced marked depolarizations of these terminals. Bethanechol (10 μm) depressed the amplitude of fast excitatory postsynaptic potentials (e.p.s.ps) recorded in low Ca2+‐high Mg2+ solution, without depolarizing ganglion cells. The quantal content measured from these fast e.p.s.ps by the variance method showed a significant reduction. Amplitudes of both miniature e.p.s.ps and ACh‐potentials induced by iontophoresis of ACh were not affected by addition of bethanechol (10 μm). The depressant effect of bethanechol (10 μm) on fast e.p.s.ps disappeared in the presence of atropine (3 μm). Atropine (3 μm) increased the quantal content measured from fast e.p.s.ps recorded in low Ca2+‐high Mg2+ solution. The depressant effect of bethanechol (10 μm) on fast e.p.s.ps was unaffected by α‐adrenoceptor blocking agents (phenoxybenzamine (10 μm) or phentolamine (10 μm)). These results suggest that presynaptic nerve terminals in bullfrog sympathetic ganglia possess a muscarinic receptor which inhibits active release of ACh.

We aimed evaluate 18F-fluorodeoxyglucose uptake at major joints for differentiating patients with rheumatoid arthritis (RA) from those with non-RA arthritis using 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET).Eighteen patients with RA (13 women; age, 66.8 ± 13.2 years) and 17 patients with non-RA (6 women; age, 50.8 ± 12.5 years) were included. Twelve joints of each patient were examined: shoulder, elbow, wrist, hip, knee, and ankle on both sides. A visual scoring (VS) system was used; quantitative parameters such as maximum standardized uptake value (SUVmax), metabolic active volume (MAV), and total lesion glycolysis (TLG) were evaluated. Total score and value of each parameter were compared between the RA and non-RA groups.Total VS score (mean, 37.7 ± 9.0 vs 21.9 ± 7.2; P < .0001) and SUVmax (mean, 28.1 ± 8.5 vs 17.9 ± 5.8; P < .001) were significantly higher in the RA group than in the non-RA group. A significant between-group difference was also observed with respect to total MAV (608.3 ± 370.7 vs 176.5 ± 217.8; P < .001) and total TLG (1139.3 ± 759.1 vs 289.5 ± 395.4; P < .001). Receiver operating characteristic curve analysis revealed that total VS had the highest area under curve (.92), with sensitivity and specificity of 88.9% and 76.4%, respectively.Quantitative PET parameters could differentiate RA from non-RA. Total VS score, however, appears to be the best convenient qualitative tool for diagnosing RA.