title: Bronchopulmonary C-fibers' IL1RI contributes to the prolonged apneic response to intra-atrial injection of capsaicin by prenatal nicotinic exposure in rat pups.
abstract: Prenatal nicotinic exposure (PNE) as a SIDS model reportedly sensitizes bronchopulmonary C-fibers (PCFs), contributing to the prolonged PCF-mediated apnea in rat pups, but the relevant mechanisms are not fully understood. Pulmonary IL-1β upregulated by cigarette smoke is known to stimulate or sensitize PCFs acting via IL-1 type I receptor (IL1RI) and inhibit inspiration frequency. Because of its upregulation observed in SIDS victims, we hypothesized that PNE increased pulmonary IL-1β release and IL1RI expression in pulmonary C-neurons via action on α7 nicotinic acetylcholine receptors (α7nAChR) to induce the prolonged PCF-mediated apnea. IL-1β in BALF and IL1RI in the nodose/jugular (N/J) ganglion and vagal pulmonary C-neurons retrogradely-traced were compared between Ctrl (saline) and PNE pups and among the vehicle-treated Ctrl and PNE and methyllycaconitine (a selective α7nAChR antagonist)-treated PNE pups. The effect of IL-1RI blockade (IL-1Ra) on the PCF-mediated apnea was also compared between Ctrl and PNE pups. PNE significantly elevated IL-1β in BALF and upregulated IL1RI gene and protein expression in N/J ganglia and gene in vagal pulmonary C-neurons. All of these responses were eliminated by pretreatment with blockade of α7nAChR. In addition, the prolonged PCF-mediated apnea in PNE pups was significantly shortened by right atrial bolus injection of IL-1Ra. We conclude that PNE enhances pulmonary IL-1β release and PCF IL1RI expression acting via α7nAChR in contributing to sensitization of PCFs and prolongation of the PCF-mediated apneic response.
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhuang
authors.affiliation: Pathophysiology Program, Lovelace Respiratory Research Institute, Albuquerque, NM, USA. Electronic address: fxu@lrri.org.
authors.forename: Fadi
authors.initials: F
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000139:chemically induced / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002211:Capsaicin; D005260:Female; D006325:Heart Atria; D007267:Injections; D053583:Interleukin-1beta / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D053573:Receptors, Interleukin-1 Type I / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: C580803:IL1R1 protein, rat; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D002211:Capsaicin
keywords: IL-1 type I receptor; Nodose/jugular ganglion; Pulmonary C-fiber-mediated apnea; SIDS