Toll-like receptor 4 potentiates Ca 2+-dependent secretion of electrolytes from swine tracheal glands

Koji Murakami, Tsutomu Tamada, Masayuki Nara, Soshi Muramatsu, Toshiaki Kikuchi, Masahiko Kanehira, Yoshio Maruyama, Masahito Ebina, Toshihiro Nukiwa

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Airway surface fluids are mainly secreted from submucosal glands, and play important roles in the defense of airways via the up-regulation of mucociliary transport, resulting in an exclusion of many microbes or foreign substances. Although there are many articles concerning the importance of Toll-like receptors (TLRs) in airway immune systems, whether TLRs directly cooperate with tracheal submucosal glands to increase secretion remains unknown. We investigated the effects of ligands of the three TLR subtypes (TLR2, TLR3, and TLR4) on the physiologic secretion of electrolytes by using a patch-clamp technique. Among these TLRs, only the TLR4 ligand, LPS, showed potentiating effects on acetylcholine (ACh)-induced ionic currents in a dose-dependentmanner. These potentiating effects were completely abolished by pretreatment with a specific TLR4 antagonist or the anti-TLR4 antibody. LPS per se exerted no appreciable effect on baseline currents. Next, we demonstrated the abundant expression of TLR4 in submucosal gland acinar cells by using immunofluorescent staining and RT-PCR. Furthermore, we revealed that both nitric oxide synthase inhibitors and cyclic guanosine monophosphate (cGMP)-dependent protein kinase (cGK) inhibitors abolished the LPS-induced potentiating effects completely. Analyses of fluorescence intensities, using an intracellular nitric oxide (NO) indicator, demonstrated that LPS could further increase the ACh-induced synthesis of NO. These findings suggest that TLR4 takes part in airway mucosal defense systems as a unique exogenous potentiator of electrolyte-water secretion from submucosal gland acinar cells, and that NO/cGMP/cGK signaling is involved in this rapid TLR4 signaling pathway.

Original languageEnglish
Pages (from-to)1101-1110
Number of pages10
JournalAmerican journal of respiratory cell and molecular biology
Volume45
Issue number5
DOIs
Publication statusPublished - 2011 Nov 1

Keywords

  • Clca
  • LPS
  • Nitric oxide
  • Patch-clamp
  • cGMP-dependent protein kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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