Lipopolysaccharides induce p8 mRNA expression in vivo and in vitro.
Systemic LPS endotoxin is associated with acute pancreatic damage. Whether damage results from direct interaction of LPS with pancreatic cells is unknown. We addressed that question by monitoring p8 expression in reponse to LPS, in vivo and in vitro, because overexpression of the p8 protein is a sensitive marker of pancreatic agression. For in vivo studies, rats were sacrificed at different times after a single intraperitoneal injection of LPS, and pancreas, liver, kidney, lung, brain, and intestine were processed for RNA preparation. In vitro, pancreatic acinar AR4-2J cells were cultivated with 0.1, 1, or 10 micrograms/ml LPS for 6, 12, or 24 h. p8 mRNA expression was monitored by Northern blotting. In vivo, it was strongly increased in the pancreas after 12 h of treatment and remained elevated after 24 h. It was also induced in kidney and liver, with a maximum at 6 and 12 h, respectively, but not in lung, brain, or intestine. In AR4-2J cells, basal p8 mRNA expression was very low and increased in a time- and dose-dependent manner after treatment with LPS. LPS-induced overexpression of p8 mRNA in vivo confirmed the adverse effect of endotoxemia on pancreas and its overexpression in vitro demonstrated a direct interaction of LPS with pancreatic cells.
Laboratoire de Recherche de Physiologie et Pathologie Digestives, INSERM U.315, 46 Bd de la Gaye, Marseille, 13009, France.
Y F
YF
Jiang
M I
MI
Vaccaro
F
F
Fiedler
E L
EL
Calvo
J L
JL
Iovanna
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D004268:DNA-Binding Proteins; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015533:Transcriptional Activation / Q000187:drug effects*
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D006133:Growth Substances; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C109741:Nupr1 protein, rat