title: Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with sepsis syndrome.
abstract: In addition to their role in cardiorespiratory regulation, carotid body (CB) chemoreceptors serve as sensors for inflammatory status and as a protective factor during sepsis. However, lipopolysaccharide-induced sepsis (LPS) reduces CB responsiveness to excitatory or depressant stimuli. We tested whether LPS exerts a direct effect on the carotid chemoreceptor pathway, the CB and its sensory ganglion. We determined that the rat CB and nodose-petrosal-jugular ganglion complex (NPJgc) express TLR4, TNF-α and its receptors (TNF-R1 and TNF-R2). LPS administration (15mg/kg intraperitoneally) evoked MyD88-mechanism pathway activation in CB and NPJgc, with NF-κB p65, p38 MAPK, and ERK activation. Consistently, LPS increased TNF-α and TNF-R2. Double-labeling studies showed that the aforementioned pathway occurs in TH-containing glomus cells and NPJgc neurons, components of the chemosensitive neural pathway. Thus, our results suggest that LPS acting directly through TLR4/MyD88-mechanism pathways increases TNF-α and TNF-R2 expression in the carotid chemoreceptor pathway. These results show a novel afferent pathway to the central nervous system during endotoxemia, and could be relevant in understanding sepsis pathophysiology and therapy.
authors.affiliation: Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas y Facultad de Medicina, Universidad Andres Bello, Santiago, Chile. rfernandez@unab.cl
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernández
authors.forename: Gino
authors.initials: G
authors.lastname: Nardocci
authors.forename: Felipe
authors.initials: F
authors.lastname: Simon
authors.forename: Aldo
authors.initials: A
authors.lastname: Martin
authors.forename: Alvaro
authors.initials: A
authors.lastname: Becerra
authors.forename: Carolina
authors.initials: C
authors.lastname: Rodríguez-Tirado
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Maisey
authors.forename: Claudio
authors.initials: C
authors.lastname: Acuña-Castillo
authors.forename: Paula P
authors.initials: PP
authors.lastname: Cortes
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002344:Carotid Body / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018613:Microscopy, Confocal; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009434:Neural Pathways / Q000502:physiology; D009620:Nodose Ganglion / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism* / Q000503:physiopathology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4