GZMA silencing inhibits JAK2/STAT1 pathway and improves allergic rhinitis.

Abstract

Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory disorder. This study attempts to identify AR-related differential expressed genes (DEGs) and determine potential targets for AR. We employed bioinformatics analysis to screen for hub DEGs for AR, and their performances in distinguishing AR were assessed by receiver operating characteristic (ROC) curves. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot was used to quantify Granzyme A (GZMA) in ovalbumin (OVA)-induced AR mice. TNF-α-induced cell model was utilized to assess the role of GZMA in AR, and the effect of GZMA silencing on the JAK2/STAT1 pathway was investigated in TNF-α-induced AR. We identified HIST1H2BD, RPS28, HIST1H1C, MAF, and GZMA as hub genes, all of which exhibited excellent performance in distinguishing between AR and controls (AUC > 0.800). GZMA was highly expressed in AR mice. Silencing GZMA reduced the levels of inflammatory cytokines (IL-6, IL-4 and IL-5), inhibited cell apoptosis and promoted cell proliferation in TNF-α-induced nasal mucosal epithelial cells (MIC-iCell-m024). Overexpression of GZMA exhibited the opposite effects by promoting inflammation and cell apoptosis but inhibiting proliferation. Mechanistically, silencing GZMA inhibited the phosphorylation of JAK2 and STAT1, indicating the suppression of JAK2/STAT1 pathway. This study might share new idea for AR management.