Preprotachykinin-A gene deletion regulates hydrogen sulfide-induced toll-like receptor 4 signaling pathway in cerulein-treated pancreatic acinar cells.
Pancreas
; 40(3): 444-52, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21289528
OBJECTIVE: This study aimed to determine the effect of hydrogen sulfide (H2S) on Toll-like receptor 4 (TLR4)-mediated innate immune signaling in acute pancreatitis (AP) via substance P. METHODS: Male Swiss mice were treated with hourly intraperitoneal injections of cerulein (50 µg/kg) for 10 hours. dl-propargylglycine ([PAG] 100 mg/kg, intraperitoneally), an inhibitor of H2S formation, was administered 1 hour after the induction of AP. Pancreatic acinar cells from male preprotachykinin-A gene-knockout mice (PPTA) and their wild-type counterparts were incubated with or without cerulein (10 M for 60 minutes). To better understand the effect of H2S in inflammation, acinar cells were stimulated with cerulein after addition of H2S donor, sodium hydrosulfide. In addition, cerulein-treated pancreatic acinar cells were pretreated with PAG (30 µM) for 1 hour. RESULTS: The H2S inhibitor PAG eliminated TLR4, interleukin 1 receptor-associated kinase 4, tumor necrosis factor receptor-associated factor 6, and nuclear factor-κB (NF-κB) levels in in vitro and in vivo models of cerulein-induced AP. PPTA gene deletion reduced TLR4, myeloid differentiation factor 88, interleukin 1 receptor-associated kinase 4, tumor necrosis factor receptor-associated factor 6, and NF-κB in cerulein-treated pancreatic acinar cells, whereas administration of sodium hydrosulfide resulted in a further rise in TLR4 and NF-κB levels in cerulein-treated pancreatic acinar cells. CONCLUSION: The present findings show for the first time that in AP, H2S may up-regulate the TLR4 pathway and NF-κB via substance P.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Páncreas
/
Precursores de Proteínas
/
Taquicininas
/
Receptor Toll-Like 4
/
Sulfuro de Hidrógeno
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pancreas
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Singapur
Pais de publicación:
Estados Unidos