Expression of major histocompatibility antigens in human chronic pancreatitis.

Jalleh, R. P.; Gilbertson, Janet A.; Williamson, R. C. N.; Slater, Susanna; Foster, Christopher S.

doi:10.1136/gut.34.10.1452

Cited by 38 publications

(22 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We previously demonstrated induction of acinar cell apoptosis, with infiltration of CD8 and CD4 T cells and tacrolimus, an immunosuppressant, attenuates this apoptosis and chronic inflammation in this model (Hashimoto et al, 2000;Yamada et al, 2001). Clinical investigations have demonstrated that infiltration of CD4 and CD8 T cells and high expression of major histocompatibility complex class I and class II antigens by pancreatic epithelial cells is observed in human chronic pancreatitis, suggesting that cell-mediated autoimmune mechanisms are at work (Anderson et al, 1988;Bedossa et al, 1990;Jalleh et al, 1993;Yoshida et al, 1995). Furthermore, autoimmune chronic pancreatitis has been recognized as a new entity in humans defined in terms of lymphocyte infiltration, autoantibody production, and effectiveness of steroid administration (Okazaki et al, 2000).…”

Section: Discussionmentioning

confidence: 74%

Candesartan, an Angiotensin II Receptor Antagonist, Suppresses Pancreatic Inflammation and Fibrosis in Rats

Yamada¹,

Kuno²,

Masuda³

et al. 2003

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists attenuate fibrosis in the kidney, heart, and liver by suppressing transforming growth factor-␤1 mRNA and decreasing production of extracellular matrix proteins. We recently demonstrated that lisinopril, an angiotensin-converting enzyme inhibitor, alleviates pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori rats. The involvement of angiotensin II receptor and its receptor interaction in the pathogenesis of spontaneous chronic pancreatitis was assessed in this model. Candesartan, an angiotensin II receptor antagonist, was administered in drinking water (10.5, 42, or 125 mg/l) to 10-week-old male WBN/Kob rats for 10 weeks and inflammatory parameters, fibrosis, and gene expression of renin-angiotensin system components and transforming growth factor-␤1 were assessed in the pancreas. Immunostaining for ␣-smooth muscle actin was also performed. Candesartan significantly suppressed decrease in pancreatic weight and increases in pancreatic myeloperoxidase activity, hydroxyproline content, ratio of fibrous tissue, histologic scores, and ratio of ␣-smooth muscle actin-positive cells (activated pancreatic stellate cells) at 20 weeks. The high dose enhanced the expression of angiotensinogen and angiotensin II receptor type 2 mRNA and suppressed the overexpression of transforming growth factor-␤1 mRNA. The conclusion is that candesartan alleviates chronic pancreatitis and fibrosis by suppressing the overexpression of transforming growth factor-␤1, resulting in prevention of activation of pancreatic stellate cells in male WBN/Kob rats. We propose that angiotensin II receptor type 1 antagonists may be useful for the treatment of chronic pancreatitis involving angiotensin II interaction with its receptor.The renin-angiotensin system (RAS) plays an important role in regulation of the systemic blood pressure, body fluid, and electrolyte balance. Angiotensin II (AT-II), an octapeptide produced by proteolytic cleavage of its precursor angiotensin I by the angiotensin-converting enzyme (ACE), is a physiologically active product of the RAS (Matsusaka and Ichikawa, 1997). It stimulates the proliferation of mesangial cells, cardiac fibroblasts, and hepatic stellate cells (HSCs) and their increased synthesis of extracellular matrix proteins through induction of transforming growth factor (TGF)-␤1 expression both in vivo and in vitro (Matsusaka and Ichikawa, 1997;Bataller et al., 2000).Two subtypes of AT-II receptors, namely, type 1 (AT1 receptor) and type 2 (AT2 receptor) have been identified (Matsusaka and Ichikawa, 1997;Matsubara, 1998). AT1 receptor, which mediates most of the biological results of AT-II action, including vasoconstriction, cell proliferation, and production of extracellular matrix proteins, is found in the kidney, liver, adrenal cortex, and blood vessels. It is well documented that AT-II induces cell hypertrophy and ion transport in the kidney, heart, and liver, primarily through AT1 receptor (Matsusaka and Ichikawa, 1...

show abstract

Section: Discussionmentioning

confidence: 74%

Candesartan, an Angiotensin II Receptor Antagonist, Suppresses Pancreatic Inflammation and Fibrosis in Rats

Yamada¹,

Kuno²,

Masuda³

et al. 2003

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…These cell types include B lymphocytes, activated T lymphocytes and macrophages, dendritic cells, glial cells, and thymic epithelial cells. Yet in certain autoimmune diseases, immune activity appears to be directed against cells that inappropriately express MHC class II molecules, such as β cells in the diabetic pancreas and thyroid cells in Grave's disease (28)(29)(30). TGF-β-null mice exhibit enhanced expression of MHC class II antigens at or before the onset of the inflammatory process, but the characteristic inflammatory lesions do not develop in TGF-β-null mice crossed into the severe combined immunodeficiency background (14).…”

Section: Discussionmentioning

confidence: 99%

Loss of TGF-β signaling contributes to autoimmune pancreatitis

Hahm

Lee

et al. 2000

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…32 The number of beta cells in these islets was found to be slightly reduced. 32 Immunohistological studies revealed that the duct epithelium commonly expresses HLA-DR and cytokines such as transforming growth factors alpha and beta (TGFa, TGFb1) and fibroblast growth factor (FGF) [33][34][35][36][37][38] TGFb1 and platelet derived growth factor (PDGF) were also found in fibroblasts, macrophages and/or platelets. 28,39,40 Myofibroblasts, which were recently named pancreatic stellate cells, are identified by their positivity for smooth muscle actin and desmin 15 ( Figure 8).…”

Section: Pathologymentioning

confidence: 99%

“…28,[41][42][43] The lymphocytic infiltrate consists largely of T lymphocytes. 33,34 The remaining acinar cells stain brightly for pancreatic enzymes and pancreatic stone protein. 44,45 The nerves that appear enlarged express particularly calcitonin-gene related peptide and substance P. 46 Both the endothelial cells and endocrine beta and alpha cells show strong endothelin-1 expression in chronic pancreatitis.…”

Section: Pathologymentioning

confidence: 99%