Engulfment of gram-positive bacteria by pancreatic stellate cells in pancreatic fibrosis.
OBJECTIVE
We previously reported the finding that pancreatic stellate cells (PSCs) have a phagocytic function. The aim of the present study was to investigate whether engulfment of gram-positive bacteria by PSCs plays any role in the pathogenesis of pancreatic fibrosis.


METHODS
Rat PSCs were cultured with lipoteichoic acid (LTA) or bacteria and analyzed for α-smooth muscle actin expression and collagen secretion. Human pancreata were obtained from routine autopsies of 20 cases; a diagnosis of gram-positive sepsis was made in 10 of the cases (sepsis group), but sepsis had not been diagnosed in the other 10 cases (control group). Pancreatic tissue was stained with anti-LTA antibody, and the severity of pancreatic fibrosis was evaluated by histological scoring.


RESULTS
Bacteria and LTA were internalized into the cytoplasm of cultured PSCs. Exposure to LTA or bacteria significantly increased α-smooth muscle actin expression and collagen secretion. Blockade of toll-like receptor 2 significantly inhibited the increase in collagen secretion in response to LTA. There was no significant difference in the severity of pancreatic fibrosis between the sepsis group and the control group.


CONCLUSIONS
The fibrogenic action of PSCs seems to be more strongly associated with activation of the toll-like receptor-dependent pathway than it is with phagocytosis of bacteria by PSCs.
Morishita
Keiichi
K
Department of Gastroenterology, School of Medicine, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan.
Shimizu
Kyoko
K
Haruta
Ikuko
I
Kawamura
Shunji
S
Kobayashi
Makio
M
Shiratori
Keiko
K
D000818:Animals; D002478:Cells, Cultured; D005355:Fibrosis; D006094:Gram-Positive Bacteria / Q000472:pathogenicity*; D008070:Lipopolysaccharides / Q000032:analysis / Q000494:pharmacology; D008297:Male; D010179:Pancreas / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000382:microbiology / Q000502:physiology*; D010587:Phagocytosis; D051381:Rats; D017208:Rats, Wistar; D013682:Teichoic Acids / Q000032:analysis / Q000494:pharmacology; D051195:Toll-Like Receptor 2 / Q000502:physiology
D008070:Lipopolysaccharides; D013682:Teichoic Acids; C495343:Tlr2 protein, rat; D051195:Toll-Like Receptor 2; C009900:lipoteichoic acid