Immunohistochemical study of transforming growth factor β1, matrix metalloproteinase-2,9, tissue inhibitors of metalloproteinase-1,2, and basement membrane components at pancreatic ducts in chronic pancreatitis

Little is known about the pathogenesis of fibrosis in chronic pancreatitis. To reach a better understanding of this problem, we investigated the immunolocalizations of type TV collagen (Col-IV) and laminin around pancreatic ducts, and those of matrix metalloproteinase-2,9 (MMP-2,9), tissue inhibitors of metalloproteinase-1,2 (TIMP-1,2), and transforming growth factor-pi (TGF beta 1) at the ductal epithelia in chronic pancreatitis. This study included 20 surgical specimens of fibrotic pancreas from patients with chronic pancreatitis and five normal samples from autopsy cases. Immunostaining was performed by the streptavidin-biotin method after antigen retrieval. We evaluated the staining patterns and the percentage of positive cells of each antigen. In chronic pancreatitis, the immunostainings of Col-IV and laminin along the basement membrane (BM) of pancreatic ducts were disrupted in 11 (55%) of 20 and eight (40%) of 20, respectively, whereas no disruption was detected in normal pancreas. Positive immunostainings for MMP-2, MMP-9, TIMP-1, and TIMP-2 in ductal epithelia were 15 (75%) of 20, five (25%) of 20, four (20%) of 20, and 10 (50%) of 20, respectively, whereas no immunostaining was seen in normal pancreas. The staining intensity of MMP-2 in ductal epithelia was associated with the staining intensity of Col-IV around the pancreatic ducts. Also, the staining intensity of MMP-2 was progressively increased in proportion to the staining intensity of TGF beta 1. These findings suggest that TGF beta 1 induced in pancreatic duct cells also induced MMP-2 in an autocrine or paracrine manner, and that this MMP-2 decomposed Col-IV of the BM of pancreatic ducts in chronic pancreatitis.