There is increasing recognition that
neurotrophin (NT) signaling occurs in non-neuronal tissues, including
airway smooth muscle (ASM). We recently demonstrated that NTs, such as
brain-derived neurotrophic factor (
BDNF), enhance
intracellular Ca(2)(+) ([Ca(2+)](i)) and force regulation in human ASM. Increased NT expression has been observed in
airway diseases, such as
asthma and
allergy. In the present study, we tested the hypothesis that NTs contribute to inflammation-induced enhancement of ASM
contractility. Using human ASM cells and real-time
fluorescence [Ca(2+)](i) imaging, we examined the contribution of the high-affinity tropomyosin-related
kinase and low-affinity, pan-NT p75NTR receptors to [Ca(2+)](i) regulation under control conditions and after exposure to the
proinflammatory cytokine TNF-alpha (20 ng/ml). Exposure to
TNF-alpha enhanced [Ca(2+)](i) responses to
agonist (
acetylcholine,
histamine). Exposure to 10 nM
BDNF for even 30 minutes substantially and synergistically enhanced
TNF-alpha effects on [Ca(2+)](i) responses to
agonist.
Small interfering RNA suppression of tropomyosin-related
kinase substantially blunted the effect of
BDNF on [Ca(2+)](i) responses to
agonist (with greater effect on Ca(2+) influx via store-operated Ca(2+) entry compared with
sarcoplasmic reticulum Ca(2+) release) in both control and TNF-alpha-exposed cells. However, p75NTR suppression by small interfering
RNA had no significant effect on [Ca(2+)](i) responses in either cell group. These novel data demonstrate that NTs influence ASM
contractility, and suggest a potential role for NTs in
airway diseases.
