title: Autoimmune pancreatitis: expression and cellular source of profibrotic cytokines and their receptors.
abstract: Chronic pancreatitis is a fibrogenic disease. In autoimmune pancreatitis (AIP), a lymphoplasmacytic infiltration is followed by fibrosis. In vitro it has been shown that pancreatic stellate cells are transformed into proliferating myofibroblasts mainly by transforming growth factor beta (TGF-beta) and platelet-derived growth factor (PDGF). We studied the expression of these profibrotic cytokines, their receptors, and their cellular sources in AIP. Pancreatic tissues from 21 patients with AIP of different grades of severity were selected from a series of 52 AIP cases. Myofibroblasts (ie, activated pancreatic stellate cells), macrophages, lymphocytes, plasma cells, and the cytokines latency-associated peptide, a TGF-beta1 propeptide, TGF-beta receptor II (TGF-beta-RII), PDGF-B, and the alpha and beta isoforms of the PDGF receptor (PDGF-R alpha and PDGF-R beta) were identified immunohistochemically. Their expression and cellular distribution were related to the severity of AIP. In grade 1 and 2 AIP, macrophages and myofibroblasts expressing profibrotic cytokines and their receptors were found in periductal areas showing lymphoplasmacytic inflammation. In grade 3 AIP, there were numerous macrophages, myofibroblasts, and epithelial cells which were positive for latency-associated peptide, PDGF-B, TGF-beta-RII, PDGF-R alpha, and PDGF-R beta not only in periductal, but also in interlobular and intralobular areas. In grade 4 AIP, which is characterized by advanced fibrosis, cellularity and expression of cytokines and their receptors were greatly reduced. Our data indicate that in AIP the occurrence of myofibroblasts is intimately related to the presence of macrophages and lymphoplasmacytic cells. These cells and adjacent epithelial cells express profibrotic cytokines and their receptors, which are probably responsible for the initiation and maintenance of the fibrogenic process.
authors.affiliation: Department of Pathology, University of Kiel, Kiel, Schleswig-Holstein, Germany.
authors.forename: Sönke
authors.initials: S
authors.lastname: Detlefsen
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.forename: Jingbo
authors.initials: J
authors.lastname: Zhao
authors.forename: Asbjørn Mohr
authors.initials: AM
authors.lastname: Drewes
authors.forename: Günter
authors.initials: G
authors.lastname: Klöppel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010982:Platelet-Derived Growth Factor; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II