Figure 5
The interaction between IL-33 and ST2 is necessary for the development of chronic pancreatitis induced by a low-dose cerulein and NOD1 ligand. C57BL6 mice were administered a low-dose cerulein (CER) for a total of three times, or FK565 followed by a low-dose cerulein for a total of three times as described in Figure 1. Mice were also treated with intraperitoneal injection of control Ab (100 μg, n=3; cerulein alone group, n=5; cerulein and FK565 group) or anti-ST2 antibody (100 μg, n=3; cerulien alone group, n=5; cerulein and FK565 group) before the initiation of each treatment regimen. Mice received each regimen twice a week for a total of 14 times after which sera and pancreatic tissues were obtained. (a) Serum levels of amylase, pancreatic weight, and pathological scores of the pancreas obtained from mice three hours after the last injection of cerulein. Results are expressed as mean±s.e.m. *P<0.05, **P<0.01 as compared with mice treated with control Ab, cerulein, and FK565. (b) Representative picture of the pancreas tissue stained with H&E, magnification × 400. (c) Concentrations of cytokines and chemokines in pancreatic lysates from mice treated with FK565-cerulein chronic pancreatitis regimen and control Ab or anti-ST2 Ab were determined by ELISA. Levels of cytokines and chemokines in the pancreas are shown as values per 100 mg pancreatic tissue. Results are expressed as mean±s.e.m. *P<0.05, **P<0.01 as compared with control Ab. (d) Pancreatic levels of hydroxyproline and the numbers of α-SMA+ cells in mice treated with FK565-cerulein chronic pancreatitis regimen and control Ab or anti-ST2 Ab. **P<0.01 as compared with control Ab. (e) Representative picture of the pancreas tissue stained with anti-SMA Ab and anti-fibronectin Ab, magnification x400. Representative picture of dual immunofluorescence of the pancreas tissue stained with anti-amylase Ab (green color) or anti-pStat3 Ab (red color) or anti-pIκBα Ab (red color). Mice received FK565-cerulein chronic pancreatitis regimen with control Ab or anti-ST2 Ab. Nuclei were stained with DAPI, magnification × 800. Ab, antibody; H&E, hematoxylin and eosin; IL, interleukin; NOD1, nucleotide-binding oligomerization domain 1.
