Ozone exposure initiates a sequential signaling cascade in airways involving interleukin-1beta release, nerve growth factor secretion, and substance P upregulation.

ABSTRACT

Previous studies demonstrated that interleukin-1ß (IL-1ß) and nerve growth factor (NGF) increase synthesis of substance P (SP) in airway neurons both after ozone (O3) exposure and by direct application. It was postulated that NGF mediates O3-induced IL-1ß effects on SP. The current study specifically focused on the influence of O3 on IL-1ß, NGF, and SP levels in mice bronchoalveolar lavage fluid (BALF) and whether these mediators may be linked in an inflammatory-neuronal cascade in vivo. The findings showed that in vivo O3 exposure induced an increase of all three proteins in mouse BALF and that O3-induced elevations in both NGF and SP are mediated by the inflammatory cytokine IL-1ß. Further, inhibition of NGF reduced O3 induced increases of SP in both the lung BALF and lung tissue, demonstrating NGF serves as a mediator of IL-1ß effects on SP. These data indicate that IL-1ß is an early mediator of O3-induced rise in NGF and subsequent SP release in mice in vivo.