Ozone exposure initiates a sequential signaling cascade in airways involving interleukin-1beta release, nerve growth factor secretion, and substance P upregulation.
Previous studies demonstrated that interleukin-1β (IL-1β) 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-1β effects on SP. The current study specifically focused on the influence of O3 on IL-1β, 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-1β. 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-1β effects on SP. These data indicate that IL-1β is an early mediator of O3-induced rise in NGF and subsequent SP release in mice in vivo.
a Department of Neurobiology and Anatomy , West Virginia School of Medicine , Morgantown , West Virginia , USA.
Joshua S
JS
Barker
Zhongxin
Z
Wu
Dawn D
DD
Hunter
Richard D
RD
Dey
D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020932:Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D010126:Ozone / Q000633:toxicity*; D012137:Respiratory System / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D013373:Substance P / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000393:Air Pollutants; D053583:Interleukin-1beta; D013373:Substance P; D010126:Ozone; D020932:Nerve Growth Factor