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

doi:10.1186/1479-5876-5-63

Journal of Translational Medicine

Volume 5

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Michalski CW
Gorbachevski A
Erkan M
Reiser C
Deucker S
Bergmann F
Giese T
Weigand M
Giese NA
Friess H
Kleeff J

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Michalski CW
Gorbachevski A
Erkan M
Reiser C
Deucker S
Bergmann F
Giese T
Weigand M
Giese NA
Friess H
Kleeff J
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Research

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

Christoph W Michalski¹^,2^* , Andre Gorbachevski²^* , Mert Erkan¹^* , Carolin Reiser¹ , Stefanie Deucker² , Frank Bergmann³ , Thomas Giese⁴ , Markus Weigand⁵ , Nathalia A Giese² , Helmut Friess¹ and Jörg Kleeff¹

¹Department of Surgery, Technische Universität München, Munich, Germany

²Department of General Surgery, University of Heidelberg, Germany

³Institute of Pathology, University of Heidelberg, Germany

⁴Institute of Immunology, University of Heidelberg, Germany

⁵Department of Anaesthesiology, University of Heidelberg, Germany

author email corresponding author email* Contributed equally

Journal of Translational Medicine 2007, 5:63doi:10.1186/1479-5876-5-63


Published:	5 December 2007

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.