Lipopolysaccharide directly affects pancreatic acinar cells: implications on acute pancreatitis pathophysiology.
We have explored whether lipopolysaccharide (LPS, endotoxin) induces pancreatic injury on pancreatic acinar cells both in vivo and in vitro. Wistar male rats were treated with four intraperitoneal injections of 10 mg/kg LPS, and AR4-2J cells were exposed to increasing doses of LPS. Expression of pancreatitis-associated-protein (PAP) mRNA was strongly induced in AR4-2J cells exposed to LPS, while amylase mRNA was reduced. LPS also induced apoptosis and expression of TNF-alpha, IL-1beta, and IL-8 mRNA in AR4-2J cells. The in vivo effect of LPS showed structural signs of cellular damage, including numerous cytoplasmic vacuoles, severe nuclear alterations, and high expression of PAP mRNA. This study demonstrated that LPS induced pancreatic damage by directly affecting the pancreatic acinar cells. The role of LPS in the pathophysiology of acute pancreatitis may be partly due to the effect LPS has on the acinar cell.
Vaccaro
M I
MI
Universidad de Buenos Aires and Universidad Austral, Argentina.
Calvo
E L
EL
Suburo
A M
AM
Sordelli
D O
DO
Lanosa
G
G
Iovanna
J L
JL
D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000235:genetics; D000818:Animals; D000951:Antigens, Neoplasm; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D037181:Lectins, C-Type; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D000073718:Pancreatitis-Associated Proteins; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018746:Systemic Inflammatory Response Syndrome / Q000473:pathology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D000209:Acute-Phase Proteins; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007375:Interleukin-1; D016209:Interleukin-8; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D000073718:Pancreatitis-Associated Proteins; C000612141:REG3A protein, human; D012333:RNA, Messenger; C000612144:Reg3b protein, rat; D014409:Tumor Necrosis Factor-alpha