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Sensitizing Effects of Chronic Pretreatment with Tumor Necrosis Factor Alpha on Vagal Pulmonary Afferent Sensitivity in Mice
Author(s) -
Lin RueiLung,
Lee LuYuan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1262.13
Subject(s) - tumor necrosis factor alpha , medicine , cytokine , receptor , pathogenesis , anesthesia , capsaicin , endocrinology , inflammation
Tumor necrosis factor alpha (TNFα), a pro‐inflammatory cytokine, is known to play an important role in the pathogenesis of allergic asthma. Inhalation of TNFα can also induce airway hyperresponsiveness in healthy human subjects, but underlying mechanisms are not fully understood. A recent study in our lab has demonstrated that TNFα pretreatment induced airway inflammation and a sustained elevation of pulmonary chemoreflex sensitivity (JAP 114: 1536–43, 2013), suggesting a possible involvement of pulmonary C‐fibers, but the direct evidence is lacking. The present study investigated the effects of chronic pretreatment with TNFα on the sensitivity of vagal pulmonary afferents in anesthetized open‐chest mice, using the single‐fiber recording technique. TNFα (10 μg/kg) and vehicle were administered by intra‐tracheal instillation in treated (TNF) and control (Veh) groups, respectively. Our results showed: 1) The peak activity of pulmonary C‐fibers to a bolus right‐atrial injection of capsaicin (Cap; 0.5 μg/kg) was significantly greater in TNF group (6.52 ± 1.34 impulses/s, n=10) than Veh group (2.10 ± 0.56 impulses/s, n=12; p<0.05). 2) The same dose of Cap evoked a burst of discharge (2.44 ± 0.71 impulses/s, n=8) in 75% (6/8) of rapidly adapting receptors (RARs) studied in TNF group, but did not stimulate any of the RARs (0/9) in Veh group. 3) This sensitizing effect of TNFα was further demonstrated in the enhanced response of Ca 2+ influx to Cap in isolated vagal pulmonary sensory neurons using the Ca 2+ imaging technique, and this effect was completely absent in the mice lacking both TNF receptors (p55/p75‐null mice). In conclusion, chronic pretreatment with TNFα induced a sensitizing effect on the Cap sensitivity in both pulmonary C‐fibers and RARs, and the action was mediated through TNF receptors. These sensitizing effects of TNFα may contribute, at least in part, to the pathogenesis of airway hyperresponsiveness induced by this cytokine. Support or Funding Information Supported by NIH grants HL‐96914 and UL1TR0000117