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

BACKGROUND: The role of endoplasmic reticulum (ER) stress in the pathogenesis of allergic rhinitis (AR) remains elusive. METHODS: Real-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. RESULTS: Compared 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. CONCLUSIONS: ER 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 EVIDENCE: NA.