Feasibility of Treating Eosinophilic Chronic Rhinosinusitis Using Short-Chain Fatty Acids.

Abstract

Epithelial cell-derived cytokines play a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNPs). Short-chain fatty acids (SCFAs) are carboxylic acids with 1-6 carbon atoms that are produced by the microbiota, which play a significant role in inflammation. We evaluated the potential role of SCFAs in eosinophilic chronic rhinosinusitis (ECRS). Gene expression levels of G protein-coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3), GPR43/FFAR2, thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33 in nasal polyp (NP) tissues were analyzed using quantitative real-time polymerase chain reaction. Primary normal human bronchial epithelial (NHBE) cells were stimulated with polyinosinic-polycytidylic acid (poly(I:C)) in the presence or absence of SCFAs, and TSLP levels were measured. Immunohistochemical analysis was conducted to evaluate GPR41 expression in eosinophils and the Eol-1 human eosinophilic leukemic cell line (Eol-1 cells). The viability of Eol-1 cells treated with propionic acid was also assessed. Both GPR41 and GPR43 mRNA expression was significantly higher in ECRS-NPs than in non-ECRS-NPs. The level of TSLP mRNA expression was also significantly elevated in ECRS-NPs that correlated with eosinophil counts in NP tissues. Although poly(I:C) stimulation induced TSLP expression in NHBE cells, acetic acid, propionic acid, and butyric acid significantly suppressed TSLP expression in a concentration-dependent manner. GPR43 was expressed in eosinophils from NP tissues and Eol-1 cells. 1 mM propionic acid significantly suppressed Eol-1 cell survival. SCFAs, particularly propionic acid, may be effective in treating ECRS by suppressing TSLP expression and eosinophils. NA.