Galectin-1 induces chemokine production and proliferation in pancreatic stellate cells.
Galectin-1 is a beta-galactoside-binding lectin. Previous studies have shown that galectin-1 was expressed in fibroblasts of chronic pancreatitis and of desmoplastic reaction associated with pancreatic cancer. These fibroblasts are now recognized as activated pancreatic stellate cells (PSCs). Here, we examined the role of galectin-1 in cell functions of PSCs. PSCs were isolated from rat pancreatic tissue and used in their culture-activated phenotype unless otherwise stated. Expression of galectin-1 was assessed by Western blot analysis, RT-PCR, and immunofluorescent staining. The effects of recombinant galectin-1 on chemokine production and proliferation were evaluated. Activation of transcription factors was assessed by EMSA. Activation of MAPKs was examined by Western blot analysis using anti-phosphospecific antibodies. Galectin-1 was strongly expressed in culture-activated but not freshly isolated PSCs. Recombinant galectin-1 increased proliferation and production of monocyte chemoattractant protein-1 and cytokine-induced neutrophil chemoattractant-1. Galectin-1 activated ERK, JNK, activator protein-1, and NF-kappaB, but not p38 MAPK or Akt. Galectin-1 induced proliferation through ERK and chemokine production mainly through the activation of NF-kappaB and in part by JNK and ERK pathways. These effects of galectin-1 were abolished in the presence of thiodigalactosie, an inhibitor of beta-galactoside binding. In conclusion, our results suggest a role of galectin-1 in chemokine production and proliferation through its beta-galactoside binding activity in activated PSCs.
Masamune
Atsushi
A
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. amasamune@int3.med.tohoku.ac.jp
Satoh
Masahiro
M
Hirabayashi
Jun
J
Kasai
Kenichi
K
Satoh
Kennichi
K
Shimosegawa
Tooru
T
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D037483:Galectin 1 / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism
D018925:Chemokines; D037483:Galectin 1; D011994:Recombinant Proteins