Nicotine and acetylcholine lead to distinct modulation of gene regulation

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.