Interleukin-1beta-induced airway hyperresponsiveness enhances substance P in intrinsic neurons of ferret airway.
Interleukin (IL)-1beta causes airway inflammation, enhances airway smooth muscle responsiveness, and alters neurotransmitter expression in sensory, sympathetic, and myenteric neurons. This study examines the role of intrinsic airway neurons in airway hyperresponsiveness (AHR) induced by IL-1beta. Ferrets were instilled intratracheally with IL-1beta (0.3 microg/0.3 ml) or saline (0.3 ml) once daily for 5 days. Tracheal smooth muscle contractility in vitro and substance P (SP) expression in tracheal neurons were assessed. Tracheal smooth muscle reactivity to acetylcholine (ACh) and methacholine (MCh) and smooth muscle contractions to electric field stimulation (EFS) both increased after IL-1beta. The IL-1beta-induced AHR was maintained in tracheal segments cultured for 24 h, a procedure that depletes SP from sensory nerves while maintaining viability of intrinsic airway neurons. Pretreatment with CP-99994, an antagonist of neurokinin 1 receptor, attenuated the IL-1beta-induced hyperreactivity to ACh and MCh and to EFS in cultured tracheal segments. SP-containing neurons in longitudinal trunk, SP innervation of superficial muscular plexus neurons, and SP nerve fiber density in tracheal smooth muscle all increased after treatment with IL-1beta. These results show that IL-1beta-enhanced cholinergic airway smooth muscle contractile responses are mediated by the actions of SP released from intrinsic airway neurons.
Wu
Z-X
ZX
Department of Neurobiology and Anatomy, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506, West Virginia 26506, USA.
Satterfield
B E
BE
Fedan
J S
JS
Dey
R D
RD
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005289:Ferrets; D007322:Instillation, Drug; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D013373:Substance P / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000503:physiopathology*
D007375:Interleukin-1; D016210:Methacholine Chloride; D013373:Substance P; D000109:Acetylcholine