Hypoxia activates SUMO-1-HIF-1α signaling pathway to upregulate pro-inflammatory cytokines and permeability in human tonsil epithelial cells

Adenoid hypertrophy (AH) can cause harmful effects on untreated children, which include mouth breathing, chronic intermittent hypoxia, sleep disordered breathing (SDB), and even some behavioral problems. However, the molecular mechanisms underlying this pathophysiological process have remained poorly understood. In study, SUMO was induced silencing overexpression using RNAi lentiviral-mediated vector. FITC-Dextran TEER were performed to examine role of in cell permeability. Co-immunoprecipitation (Co-IP) assay interaction between SUMO1 HIF-1α. Immunohistochemistry staining used expressions ZO-1, Claudin-1 occluding respectively. We found that a hypoxic condition caused dramatic upregulation SUMO-1 expression time-dependent manner, member ubiquitin-like protein family. Knockdown deeply suppressed secretions pro-inflammation cytokines including IL-6, IL-8, TNF-α, decreased permeability HTECs. Moreover, HIF-1α inhibitor 2-MeOE2 abolished function Furthermore, results obtained from CO-IP had suggested interacted with HIF-1α, prevented its ubiquitination degradation HTECs by sumoylating. Importantly, our data showed hypoxia-induced inflammation markedly inhibited M2 macrophages possess potent anti-inflammatory function. Our suggest selectively inhibiting SUMO-1-HIF-1α signaling pathway leads responses human tonsil epithelial cells, might be novel therapeutic approach for managing SDB resulting AH.