Endoplasmic reticulum stress promotes local immunoglobulin E production in allergic rhinitis.

Abstract

BackgroundThe role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive.MethodsReal‐time polymerase chain reaction (RT‐PCR), immunohistochemistry, and western blotting analyses were performed to detect the expression of ER stress and unfolded protein response markers: 78‐kDa glucose‐regulated protein (GRP78), C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6α), spliced X‐box binding protein 1 (sXBP‐1), and phosphorylated eukaryotic initiation factor 2α (p‐eIF2α), in inferior turbinate tissue samples from patients with AR and non‐AR controls. Nasal tissues from patients with AR were cultured ex vivo and treated with 4‐phenylbutyric acid (4‐PBA), an ER stress inhibitor.ResultsCompared to those in non‐AR controls, the mRNA and protein levels of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α were significantly increased in nasal tissues from patients with AR. GRP78 and CHOP were mainly expressed in CD138+ plasma cells in nasal tissues from patients with AR. The frequency of IgE+CD138+ plasma cells was significantly higher in nasal tissues from patients with AR than that in non‐AR controls. IgE levels in nasal secretions and tissues were positively correlated with GRP78 and CHOP mRNA levels in the nasal tissues. After 4‐PBA treatment, the protein expression of GRP78, CHOP, ATF6α, sXBP‐1, and p‐eIF2α was significantly reduced in cultured AR‐derived nasal tissues, and IgE levels were simultaneously decreased in cultured supernatants.ConclusionsER stress may be involved in the regulation of local IgE production in patients with AR. Inhibition of ER stress potentially provides a therapeutic avenue in AR by reducing local IgE production.Level of EvidenceNA