Exposure to environmental black carbon exacerbates nasal epithelial inflammation via the reactive oxygen species (ROS)-nucleotide-binding, oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3)-caspase-1-interleukin 1β (IL-1β) pathway.

Abstract

Allergic rhinitis(AR) is an increasing challenge to public health worldwide. Exposure to environmental black carbon (BC) is associated with increased risk of allergic rhinitis, but the molecular mechanisms underlying its toxicity have not been fully elucidated. The aims of the present study were therefore to determine the effect of BC on the expression of interleukin 1β (IL-1β) and to investigate the mechanism underlying BC-induced IL-1β production in pollen-sensitized human nasal epithelial cells (hNECs). Nasal mucosal samples collected from 10 patients undergoing nasal surgery were used to isolate and culture epithelial cells as air-liquid interface (ALI) cultures. Cultures exposed to BC ± pollen allergen for 24 hours were assessed for the presence of IL-1β, the production of reactive oxygen species (ROS), and activation of the nucleotide-binding, oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Furthermore, the mechanisms underlying BC ± pollen allergen-induced IL-1β in hNECs were evaluated. Exposure to BC significantly increased the production of IL-1β and ROS and the expression of NLRP3 in hNECs, compared with control, all of which were significantly increased further by exposure to a combination of BC and pollen. Incubation of hNECs with N-acetyl-L-cysteine (NAC) significantly attenuated BC ± pollen-induced expression of ROS, NLRP3, and IL-1β. NLRP3 and Caspase-1 inhibitors (MCC950 and YVAD) significantly inhibited IL-1β expression and NLRP3 activation, but not NLRP3 expression following exposure to BC ± pollen. These findings suggest that exposure to BC and pollen can exaggerate oxidative stress and significantly increase the expression of IL-1β in hNECs, and that this may involve a pathway integrating ROS-NLRP3-Caspase-1-IL-1β signaling.