Nicotine and acetylcholine lead to distinct modulation of gene regulation

Jochen Steppan, Stefan Hofer, Siegfried Lang, Thorsten Brenner, Eike Martin, Martina Brueckmann, Markus A. Weigand

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)124-130
Number of pages7
JournalApplied Cardiopulmonary Pathophysiology
Volume14
Issue number2
Publication statusPublished - 2010
Externally publishedYes

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Keywords

  • EGF
  • Gene chips
  • Gene regulation
  • Sepsis
  • TXNIP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)

Cite this

Steppan, J., Hofer, S., Lang, S., Brenner, T., Martin, E., Brueckmann, M., & Weigand, M. A. (2010). Nicotine and acetylcholine lead to distinct modulation of gene regulation. Applied Cardiopulmonary Pathophysiology, 14(2), 124-130.