PT  - JOURNAL ARTICLE
AU  - Koji Murakami
AU  - Tsutomu Tamada
AU  - Masayuki Nara
AU  - Soshi Muramatsu
AU  - Toshiaki Kikuchi
AU  - Masahiko Kanehira
AU  - Masahito Ebina
TI  - TLR4 signaling potentiates airway secretion from the swine submucosal gland via NO/cGMP/cGK pathway
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P3409
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P3409.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P3409.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - [RATIONALE] Airway secretion plays an important role in the airway defense as a part of innate immunity. A major fraction of the airway fluids appears to be derived from submucosal gland in response to ACh. Toll-like receptor 4 (TLR4) recognizes gram-negative bacteria and activates the innate immune systems. However, the biological role of TLR4 in the airway secretion is not well understood.[METHODS] Freshly isolated swine tracheal submucosal gland cells were investigated their secretory activities as ionic currents by applying a patch-clamp technique. LPS was used as a potent TLR4 ligand. The expression of TLR4 was estimated by both the immunofluorescent staining and RT-PCR. The involvement of NO/cGMP/cGMP-dependent protein kinase (cGK) pathway was investigated by applying both the NOS and cGK inhibitors. The synthesis of endogenous NO was estimated by an intracellular NO indicator, DAF-2DA.[RESULTS] LPS significantly potentiated the ACh-evoked ionic currents. This potentiating effect was completely abolished by the pretreatment of anti-TLR4 antibody or TLR4 antagonist. The immunofluorescent staining and RT-PCR revealed the abundant expression of TLR4 on tracheal submucosal glands. Two different inhibitors of each NOS and cGK completely abolished the LPS-induced potentiating effect, respectively. LPS further increased the ACh-induced synthesis of NO.[CONCLUSIONS] Our studies revealed that TLR4 signaling could potentiate the electrolyte and water secretions from tracheal submucosal glands via the activation of NO/cGMP/cGK pathway. These findings suggest that TLR4 takes part in the airway mucosal innate immune systems as one of important pathogen-specific secretagogue.