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Corticosteroids inhibit anti-IgE activities of specialized proresolving mediators on B cells from asthma patients
Nina Kim, … , Patricia J. Sime, Richard P. Phipps
Nina Kim, … , Patricia J. Sime, Richard P. Phipps
Published February 9, 2017
Citation Information: JCI Insight. 2017;2(3):e88588. https://doi.org/10.1172/jci.insight.88588.
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Research Article Immunology Inflammation

Corticosteroids inhibit anti-IgE activities of specialized proresolving mediators on B cells from asthma patients

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Abstract

Specialized proresolving mediators (SPMs) promote the resolution of inflammation and exert beneficial effects in animal models of chronic inflammatory diseases, including asthma. Previously, we have shown that certain SPMs reduce IgE production in B cells from healthy individuals, which has a critical role in allergic asthma. Here, we investigated the effects of SPMs on B cell IgE production in asthma patients. Peripheral blood mononuclear cells from asthma patients were treated with 17-HDHA or RvD1, and IgE levels were measured. RvD1 and 17-HDHA dampened IgE production in B cells from most asthma patients, whereas B cells from a subset of patients taking oral steroids were refractory to SPM treatment. Molecular mechanisms underlying the interaction between corticosteroids and SPMs were investigated by treating B cells from nonasthmatic donors with corticosteroids in vitro. Corticosteroids blocked the inhibitory effects of 17-HDHA and RvD1 on B cell IgE production by abolishing the suppressive activity of these mediators on IgE class switching. Corticosteroids decreased the expression of transcriptional repressor Bcl-6 as well as its suppressive activity on epsilon germline transcription. We conclude that 17-HDHA and RvD1 can reduce IgE production in asthma patients not taking high doses of steroids but that corticosteroids interfere with the ability of B cells to respond to proresolving mediators.

Authors

Nina Kim, Thomas H. Thatcher, Patricia J. Sime, Richard P. Phipps

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Figure 1

17-HDHA and RvD1 reduce spontaneous B cell IgE production from asthma patients.

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17-HDHA and RvD1 reduce spontaneous B cell IgE production from asthma pa...
(A) PBMCs from asthma or nonasthmatic donors were cultured in 96-well plates for 6 days, and IgE levels in cell culture supernatants were measured by ELISA. (B) PBMCs from 5 asthma patients were pretreated with 17-HDHA or RvD1 and incubated for 6 days. The SPMs were added daily until day 6 when cell culture supernatants were collected to measure IgE levels. Each symbol represents an individual donor and represents means of triplicates. Data were analyzed by repeated-measures 1-way ANOVA with Tukey’s post test, *P ≤ 0.05, ***P ≤ 0.001. PBMC, peripheral blood mononuclear cell; SPM, specialized proresolving mediator.

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