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Mononuclear cells modulate the activity of pancreatic stellate cells which in turn promote fibrosis and inflammation in chronic pancreatitis

Michalski, Christoph W. ; Gorbachevski, Andre ; Erkan, Mert ; Reiser, Carolin ; Deucker, Stefanie ; Bergmann, Frank ; Giese, Thomas ; Weigand, Markus ; Giese, Nathalia A. ; Friess, Helmut ; Kleeff, Jörg

In: Journal of Translational Medicine, 5 (2007), Nr. 63. pp. 1-11. ISSN 1479-5876

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Download (2MB) | Lizenz: Creative Commons LizenzvertragMononuclear cells modulate the activity of pancreatic stellate cells which in turn promote fibrosis and inflammation in chronic pancreatitis by Michalski, Christoph W. ; Gorbachevski, Andre ; Erkan, Mert ; Reiser, Carolin ; Deucker, Stefanie ; Bergmann, Frank ; Giese, Thomas ; Weigand, Markus ; Giese, Nathalia A. ; Friess, Helmut ; Kleeff, Jörg underlies the terms of Creative Commons Attribution 3.0 Germany

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Abstract

Background: Interactions between mononuclear cells and activated pancreatic myofibroblasts (pancreatic stellate cells; PSC) may contribute to inflammation and fibrosis in chronic pancreatitis (CP). Methods: Markers of fibrosis and inflammation were concomitantly analysed by immunohistochemistry in chronic pancreatitis tissues. In vitro, PSC were stimulated with TNFalpha and LPS. Primary human blood mononuclear cells (PBMC) and PSC were cocultured, followed by analysis of cytokines and extracellular matrix (ECM) proteins. PBMC were derived from healthy donors and CP and septic shock patients. Results: In areas of mononuclear cell infiltration in chronic pancreatitis tissues, there was decreased immunoreactivity for collagen1 and fibronectin, in contrast to areas with sparse mononuclear cells, although PSC were detectable in both areas. LPS and TNFalpha induced collagen1 and fibronectin levels as well as the matrix degradation enzyme MMP-1. Coculture experiments with PSC and PBMC revealed increased fibronectin secretion induced by PBMC. In addition, donor and CP PBMC significantly induced an increase in IL-6, MCP-1 and TGFbeta levels under coculture conditions. Determination of the source of cytokines and ECM proteins by mRNA expression analysis confirmed PSC as major contributors of ECM production. The increase in cytokine expression was PBMC- and also PSC-derived. Conclusion: Mononuclear cells modulate the activity of pancreatic stellate cells, which may in turn promote fibrosis and inflammation.

Item Type: Article
Journal or Publication Title: Journal of Translational Medicine
Volume: 5
Number: 63
Publisher: BioMed Central
Place of Publication: London
Date Deposited: 25 Jan 2016 09:47
Date: 2007
ISSN: 1479-5876
Page Range: pp. 1-11
Faculties / Institutes: Medizinische Fakultät Heidelberg > Chirurgische Universitätsklinik
Medizinische Fakultät Heidelberg > Universitätsklinik für Anaesthesiologie
Medizinische Fakultät Heidelberg > Institut für Immunologie
Medizinische Fakultät Heidelberg > Pathologisches Institut
Subjects: 610 Medical sciences Medicine
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