eprintid: 19645
rev_number: 15
eprint_status: archive
userid: 1589
dir: disk0/00/01/96/45
datestamp: 2016-01-25 09:47:22
lastmod: 2016-02-01 09:55:09
status_changed: 2016-01-25 09:47:22
type: article
metadata_visibility: show
creators_name: Michalski, Christoph W.
creators_name: Gorbachevski, Andre
creators_name: Erkan, Mert
creators_name: Reiser, Carolin
creators_name: Deucker, Stefanie
creators_name: Bergmann, Frank
creators_name: Giese, Thomas
creators_name: Weigand, Markus
creators_name: Giese, Nathalia A.
creators_name: Friess, Helmut
creators_name: Kleeff, Jörg
title: Mononuclear cells modulate the activity of pancreatic stellate cells which in turn promote fibrosis and inflammation in chronic pancreatitis
subjects: ddc-610
divisions: i-910200
divisions: i-910300
divisions: i-911600
divisions: i-912000
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.  
date: 2007
publisher: BioMed Central
id_scheme: DOI
id_number: http://dx.doi.org/10.1186/1479-5876-5-63
ppn_swb: 1653712406
own_urn: urn:nbn:de:bsz:16-heidok-196456
language: eng
bibsort: MICHALSKICMONONUCLEA2007
full_text_status: public
publication: Journal of Translational Medicine
volume: 5
number: 63
place_of_pub: London
pagerange: 1-11
issn: 1479-5876
citation:   Michalski, Christoph W. ; Gorbachevski, Andre ; Erkan, Mert ; Reiser, Carolin ; Deucker, Stefanie ; Bergmann, Frank ; Giese, Thomas ; Weigand, Markus ; Giese, Nathalia A. ; Friess, Helmut ; Kleeff, Jörg  (2007) Mononuclear cells modulate the activity of pancreatic stellate cells which in turn promote fibrosis and inflammation in chronic pancreatitis.  Journal of Translational Medicine, 5 (63).  pp. 1-11.  ISSN 1479-5876     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/19645/1/12967_2007_Article_223.pdf