ORIGINAL ARTICLE

The ECM proteoglycan decorin links desmoplasia and inflammation in chronic pancreatitis

J Köninger¹, N A Giese¹, M Bartel¹, F F di Mola¹, P O Berberat¹, P di Sebastiano¹, T Giese², M W Büchler¹, H Friess¹

¹ Division of Pancreatic Surgery and Molecular Pancreatic Research, Department of General Surgery, University of Heidelberg, D-69120 Heidelberg, Germany
² Department of Immunology, University of Heidelberg

Correspondence to:
Correspondence to:
Dr H Friess
Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, D-69120 Heidelberg, Germany; Helmut_Friess{at}med.uni-heidelberg.de

Background: Recurrent inflammation in chronic pancreatitis (CP) is not well understood.

Aims: To investigate whether decorin, an extracellular matrix (ECM) proteoglycan with macrophage modulating activity, is a pathogenic factor allowing diseased pancreatic stroma to sustain inflammation by affecting the cytokine profile of accumulating inflammatory cells.

Methods: Decorin was examined in 18 donors and 32 patients with CP by quantitative reverse transcription polymerase chain reaction (QRT-PCR), western blotting, and immunohistochemistry of pancreatic specimens. QRT-PCR was used to assess cytokine expression in donor peripheral blood mononuclear cells (PBMC), exposed or not to decorin in vitro, and to compare it with the cytokine profile of circulating and resident mononuclear cells (MNC) of patients with CP.

Results: In CP, desmoplasia is associated with overexpression of decorin in the growing ECM and enlarged pancreatic nerves. In culture, exposure of MNC to decorin stimulated expression of the MNC recruiting chemokine MCP-1. In biopsies, MNC infiltrates in decorin rich CP tissue showed a 300-fold upregulation of MCP-1 compared with decorin free peripheral blood, whereas no difference was found in basal MCP-1 expression in PBMC of patients versus donors. This effect was specific for MCP1—other inflammatory cytokines, such as interleukin 1ß and tumour necrosis factor , were not affected.

Conclusion: Decorin is a molecular marker of desmoplasia in CP, and excessive decorin may allow fibrotic masses to nourish and protract inflammation by deregulating the process of MNC accumulation and activation. These data provide a molecular basis for surgical resection of diseased tissue as a treatment option in CP.

Abbreviations: CP, chronic pancreatitis; CPB, cyclophillin B; ECM, extracellular matrix; IL, interleukin; HPRT, hypoxanthine phosphoribosyl transferase; MCP-1, monocyte chemoattracting protein 1; MNC, mononuclear cells; PBMC, peripheral blood mononuclear cells; TBS, Tris buffered saline; TGFß1, transforming growth factor ß1; Th1/2, T helper type 1/2; TNF, tumour necrosis factor ; QRT-PCR, quantitative reverse transcription polymerase chain reaction

Keywords: extracellular matrix; decorin; MCP1; chronic pancreatitis; chronic inflammation

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