Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with sepsis syndrome

Ricardo Fernández, Gino Nardocci, Felipe Simon, Aldo Martin, Alvaro Becerra, Carolina Rodríguez-Tirado, Kevin R. Maisey, Claudio Acuña-Castillo, Paula P. Cortes

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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 (15. mg/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.

Original languageEnglish
Pages (from-to)336-348
Number of pages13
JournalRespiratory Physiology and Neurobiology
Volume175
Issue number3
DOIs
StatePublished - 15 Mar 2011
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grants DI-02-06/R and DI-39-09/R (to RF), and DI 40-09/R (to FS) from the Division for Research of the Universidad Andres Bello (UNAB) . Thanks are due to Ms. Valentina Squicciarini and to Mr. Patrick Alvarez, for their assistance during some experiments. Special thanks go to Mr. George Montgomery for proofreading the manuscript.

Keywords

  • Carotid body
  • LPS
  • MyD88-dependent
  • Sepsis
  • TLR4
  • TNF-α

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