Increased expression of hCLCA1 in chronic rhinosinusitis and its contribution to produce MUC5AC

Objectives/Hypothesis: Mucus hypersecretion is a hallmarks of chronic rhinosinusitis. The expression of MUC5AC, a major respiratory mucin gene, is increased in chronic rhinosinusitis. The mechanisms inducing mucus hypersecretion have not been fully evaluated in chronic rhinosinusitis. Human Ca²⁺-activated Cl- channel 1 (hCLCA1) is implicated in the regulation of mucus production, airway fluid, and electrolyte transport. The present study objectives was to investigate the expression of hCLCA1 in chronic rhinosinusitis and evaluate whether its level is altered by stimulation with type 1 T helper (Th1) and Th2 cytokines, and to determine the possible role of hCLCA1 on the regulation of mucin 5AC (MUC5AC) production. Study Design: Controlled prospective study. Methods: The expression of hCLCA1 and MUC5AC in normal and inflammatory ethmoid mucosa was determined by real-time polymerase chain reaction, immunohistochemistry, and Western blot. In cultured cells, the expression of hCLCA1 and MUC5AC was measured after stimulation with Th1 and Th2 cytokines. In a supernatant, the MUC5AC level was analyzed using enzyme-linked immunosorbent assay after treatment with niflumic acid. Results: The levels of hCLCA1 and MUC5AC were increased in chronic rhinosinusitis, irrespective of nasal polyp presence, where they were distributed in superficial epithelial cells and submucosal glands. In cultured cells treated with interleukin (IL)-9, IL-4, IL-13, tumor necrosis factor-α, transforming growth factor-β, interferon-γ, and IL-1β, the expression of hCLCA1 and MUC5AC was increased. In cells treated with niflumic acid, the production of MUC5AC was inhibited. Conclusions: The current findings indicate that the expression of hCLCA1 is increased in chronic rhinosinusitis and may be regulated by Th1 and Th2 cytokines, possibly contributing to the production of MUC5AC. Level of Evidence: NA Laryngoscope, 126:E347–E355, 2016.