We studied acute effects of tumor necrosis factor-α (TNFα) on the sensitivity of isolated rat vagal pulmonary sensory neurons. Our results showed the following. First, a brief pretreatment with a low dose of TNFα (1.44 nM, 9 min) enhanced the sensitivity of transient receptor potential vanilloid type 1 (TRPV1) receptors in these neurons in two distinct phases: the inward current evoked by capsaicin was amplified (Δ -247%) immediately following the TNFα pretreatment, which gradually declined toward control and then increased again reaching another peak (Δ -384%) after 60–90 min. Second, the immediate phase of this potentiating effect of TNFα was completely abolished by a pretreatment with a selective cyclooxygenase-2 (COX-2) inhibitor, NS-398, whereas the delayed potentiation was only partially attenuated. Third, in sharp contrast, TNFα did not generate any potentiating effect on the responses to non-TRPV1 chemical activators of these neurons. Fourth, the selectivity of the TNFα action on TRPV1 was further illustrated by the responses to acid (pH 6.0); TNFα did not affect the rapid transient current mediated by acid-sensing ion channels but significantly augmented the slow sustained current mediated by TRPV1 in the same neurons. Fifth, in anesthetized rats, a similar pattern of acute sensitizing effects of TNFα on pulmonary C-fiber afferents and the involvement of COX-2 were also clearly shown. In conclusion, a brief pretreatment with TNFα induced both immediate and delayed potentiating effects on the TRPV1 sensitivity in pulmonary sensory neurons, and the production of COX-2 arachidonic acid metabolites plays a major role in the immediate sensitizing effect of TNFα.
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|State||Published - 2017|
Bibliographical noteFunding Information:
This study was supported in part by National Institutes of Health Grants HL-96914, AI-123832, and UL1-TR-001998 (to L.-Y. Lee) and Taipei Medical University Grant TMU105-AE1-B17 (to C.-C. Hsu).
© 2017 the American Physiological Society.
- Airway inflammation
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology