Differential expression of chemokines in normal pancreas and in chronic pancreatitis

Saurer, Leslie; Reber, P. U.; Schaffner, Thomas; Büchler, Markus W.; Buri, Caroline; Каппелер, Андреас; Walz, Alfred; Frieß, Helmut; Mueller, Christoph

doi:10.1016/s0016-5085(00)70218-6

Cited by 113 publications

(77 citation statements)

References 31 publications

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“…4,52,53 The chemokine MCP-1, one of the major monocyte chemoattractants, is highly expressed in fibroblasts in CP, induces TGF-b upregulation and is associated with the progression of pancreatic fibrosis. 52,54 Blocking of MCP-1 attenuates the degree of fibrosis in experimental CP. 52 Regarding fractalkine and fibrosis, CX3CR1 was identified to have a genetic and functional importance in higher stages of liver fibrosis in chronic hepatitis C, and was noticeably upregulated in patients with enhanced renal fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Ceyhan

Deucker

Demir

et al. 2009

Laboratory Investigation

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The chemokine fractalkine induces migration of inflammatory cells into inflamed tissues, thereby aggravating inflammatory tissue damage and fibrosis. Furthermore, fractalkine increases neuropathic pain through glial activation, which can be diminished by blocking of its receptor, CX3CR1, through neutralizing antibodies. As chronic pancreatitis (CP) is characterized by tissue infiltration of inflammatory cells, fibrosis, pancreatic neuritis and severe pain, the roles of fractalkine and CX3CR1 were investigated in CP (n ¼ 61) and normal pancreas (NP, n ¼ 21) by QRT-PCR, western blot and immunohistochemistry analyses. Their expression correlated with the severity of pancreatic neuritis, fibrosis, intrapancreatic nerve fiber density and hypertrophy, pain, CP duration and with the amount of inflammatory cell infiltrate immuno-positive for CD45 and CD68. To investigate the influence of fractalkine on pancreatic fibrogenesis, human pancreatic stellate cells (hPSCs) were isolated from patients with CP, incubated with fractalkine and then Collagen-1 and a-smooth muscle actin (a-SMA) expressions were measured. CX3CR1, but not fractalkine, mRNA was overexpressed in CP. In contrast, the protein levels of both CX3CR1 and fractalkine were upregulated. Neuro-immunoreactivity for fractalkine and CX3CR1 was strongest in patients suffering from severe pain and pancreatic neuritis. Long-term suffering from CP was noticeably related to increased neural immunoreactivity of fractalkine. Furthermore, fractalkine and CX3CR1 mRNA overexpressions were associated with enhanced lymphocyte and macrophage infiltration. Advanced fibrosis was associated with increased fractalkine expression, whereas in vitro fractalkine had no significant impact on collagen-1 and a-SMA expressions in hPSCs. Therefore, pancreatic fractalkine expression appears to be linked to visceral pain and to the recruitment of inflammatory cells into the pancreatic tissue and nerve fibers, with subsequent pancreatic neuritis. However, pancreatic fibrogenesis is probably indirectly influenced by fractalkine. Taken together, these novel findings suggest that CX3CR1 represents a potential novel therapeutic target to reduce inflammation and modulate pain in CP.

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Section: Discussionmentioning

confidence: 99%

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Ceyhan

Deucker

Demir

et al. 2009

Laboratory Investigation

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“…Grady T [19] found that the level of MCP-1/JE mRNA elevated in caerulin-induced experimental pancreatitis. In human AP, MCP-1 expression was found to upregulate in pancreatic tissues, and monocytic exudation was considered to be caused by this chemokine [20] . IL-8 as one of the earliest cytokines appearing in the serum of patients with AP remains persistently elevated and therefore it might be of help in assessing the severity of AP after admission [21] .…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphism of MCP-1-2518 , IL-8-251 and susceptibility to acute pancreatitis: A pilot study in population of Suzhou, China

Chen¹,

Nie²

2008

WJG

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“…These infiltrates were shown to contain activated cytotoxic T cells (Hunger et al, 1997), suggesting a role of the immune system in the pathogenesis of acinar atrophy and local scarring. Induction of HLA-DR molecules was observed in parenchymal areas affected by chronic pancreatitis (Bedossa et al, 1990;Jalleh et al, 1993) and transcripts for MCP-1 chemokine have been detected in areas of early stage of chronic pancreatitis (Saurer et al, 2000). Local expression of T cell tropic chemokines may recruit T cells, the CD4 subset of which then may cognately interact with HLA-DR neoexpressing epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Differential and Mutually Exclusive Expression of CD95 and CD95 Ligand in Epithelia of Normal Pancreas and Chronic Pancreatitis

Hasel

Rau

Perner

et al. 2001

Laboratory Investigation

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SUMMARY:Acinar regression in chronic pancreatitis may be due to immune attack in parenchymal areas neoexpressing HLA-DR molecules. CD4 ϩ Th1 cytotoxic T cells induce apoptosis of their targets via oligomerizing CD95 (APO-1/Fas) death receptors on target cells by their CD95 ligand (CD95L). We determined the expression of CD95 and CD95L in epithelia of normal and chronically inflamed pancreatic tissues. We applied RT-PCR and Western blotting for CD95L expression profiles, serial frozen section immunohistochemistry to detect CD95, CD95L, and HLA-DR molecules, CD3, CD4, CD11c, and S-100 protein (S100p). Normal pancreases and chronic pancreatitis contain CD95L message and protein. Immunohistochemistry revealed a mutually exclusive expression of CD95 and CD95L. Physiologically, acini were CD95 Ϫ /CD95L ϩ , ducts were CD95 Ϫ /CD95L Ϫ , and islets were CD95 Ϫ /CD95L ϩ . In areas of lymphohistiocytic infiltration, mainly consisting of CD3 ϩ CD4 ϩ T cells and CD11c ϩ , CD4 ϩ/Ϫ , S100p ϩ interstitial dendritic cells, and in areas of initial fibrosis, acini and ducts were HLA-DR ϩ , acini CD95 ϩ /CD95L Ϫ , and ducts CD95 ϩ /CD95L Ϫ . Islet cells were CD95 Ϫ /CD95L ϩ in both conditions. IFN␥ levels in protein lysates, as measured by an immunoassay, were significantly higher in chronic pancreatitis than in normal pancreas (p Ͻ 0.0003). In vitro, IFN␥ downmodulated CD95L message and protein in ASPC1 and BxPc3 pancreatic carcinoma cells. In conclusion, pancreatic epithelia differentially express CD95 and CD95L in a mutually exclusive manner. In chronic pancreatitis the CD95 Ϫ /CD95L ϩ status is conserved in islet cells even in the vicinity of lymphohistiocytic infiltrates, whereas it is lost in acini coexpressing HLA-DR. As a potential consequence, and possibly triggered by local release of IFN␥, CD4 ϩ Th1 cells may cognately interact with and successfully attack exocrine cells by triggering CD95 on their target without being killed by epithelial, CD95L-mediated, counterattack. (Lab Invest 2001, 81:317-326).C hronic pancreatitis is characterized by a progressive loss and fibrosis of exocrine parenchyma whereas the endocrine part of the organ remains structurally intact for a prolonged period of time (Bockman, 1997;Klöppel and Maillet, 1993;Sarles, 1991). The disease is often accompanied by duct ectasia and might be initiated by ductal obstruction or distortion (Klöppel and Maillet, 1993). Furthermore, foci of lymphohistiocytic infiltrates are commonly found and are also associated with regressing parenchyma (Bockman, 1997). These infiltrates were shown to contain activated cytotoxic T cells (Hunger et al, 1997), suggesting a role of the immune system in the pathogenesis of acinar atrophy and local scarring. Induction of HLA-DR molecules was observed in parenchymal areas affected by chronic pancreatitis (Bedossa et al, 1990;Jalleh et al, 1993) and transcripts for MCP-1 chemokine have been detected in areas of early stage of chronic pancreatitis (Saurer et al, 2000). Local expression of T cell tropic chemokines may recruit T cell...

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Differential expression of chemokines in normal pancreas and in chronic pancreatitis

Cited by 113 publications

References 31 publications

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Neural fractalkine expression is closely linked to pain and pancreatic neuritis in human chronic pancreatitis

Genetic polymorphism of MCP-1-2518 , IL-8-251 and susceptibility to acute pancreatitis: A pilot study in population of Suzhou, China

Differential and Mutually Exclusive Expression of CD95 and CD95 Ligand in Epithelia of Normal Pancreas and Chronic Pancreatitis

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