Jochen Steppan1*, Stefan Hofer1*, Siegfried Lang2, Thorsten Brenner1, Eike Martin1, Martina Brueckmann2, Markus A Weigand3
1Department of Anaesthesiology, University Hospital Heidelberg, Germany; 2Department of Medicine, University Hospital Mannheim, Germany; 3Department of Anaesthesiology, University Hospital Gießen
*contributed equally to this work
[Applied Cardiopulmonary Pathophysiology 14: 124-130, 2010]
Background: Sepsis is well known to lead to the activation of multiple pro-inflammatory markers, like MCP-1 (Monocyte chemotactic protein 1), TNF-alpha (Tumor necrosis factor alpha), while the underlying genetic changes still remain poorly studied.
Methods: We used human umbilical vein endothelial cells to test the reactions to nicotine or acetylcholine/pyridostigmine administration in regards to MCP-1 levels, gene regulation and RNR expression.
Results: Pyridostigmine and Acetylcholine (Ach) lead to a significant decrease of MCP-1 levels in TNF-alpha stimulated human umbilical vein endothelial cells, while nicotine had no effect. Interestingly nicotine and acetylcholine lead to different gene expression (nicotine up-regulates epidermal growth factor and down-regulates matrix metalloproteinase-8, while Ach/pyridostigmine up-regulates thioredoxin interacting protein and down-regulates insulin like growth factor 1). Furthermore RNA levels and gene activation were similar after nicotine administration, while changes in RNA levels after Ach/pyridostigmine differed significantly.
Conclusions: Our results suggest that the effects of Ach/pyridostigmine and nicotine are modulated by different underlying pathways, despite their common activation of nicotinergic receptors.
Key words: sepsis, gene regulation, gene chips, EGF, TXNIP
Prof. Markus A. Weigand, M.D.
Department of Anesthesiology and Intensive