Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway

• Published in: PloS one Vol. 2; no. 5; p. e469
• Main Authors: Sadis, Claude, Teske, Gwen, Stokman, Geurt, Kubjak, Carole, Claessen, Nike, Moore, Fabrice, Loi, Patrizia, Diallo, Bilo, Barvais, Luc, Goldman, Michel, Florquin, Sandrine, Le Moine, Alain
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23-05-2007; Public Library of Science (PLoS)
• Subjects: alpha7 Nicotinic Acetylcholine Receptor; Anesthesiology; Animals; Anti-inflammatory agents; Apoptosis; Arteries; Blotting, Western; Caspase; Caspase-3; Cell Proliferation; Chemokine KC; Chemokines; Comparative analysis; CXC chemokines; Damage prevention; Denervation; Endothelium; Gangrene; Gastrointestinal diseases; HMGB1 protein; Hospitals; Hydrogen-Ion Concentration; Immune response; Immunity; Immunology; Immunology/Innate Immunity; Infiltration; Inflammation; Inflammation Mediators - physiology; Inflammatory response; Injuries; Innate immunity; Ischemia; Kidney - blood supply; Kidney - drug effects; Kidney - physiopathology; Kidney transplantation; Kidneys; Laboratory animals; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nephrology/Acute Renal Failure; Nephrology/Dialysis and Renal Transplantation; Neutrophils; Nicotine; Nicotine - pharmacology; Nuclear weapons; Organ transplantation; Pathology; Phosphorylation; Pre-eclampsia; Proteins; Receptors, Nicotinic - genetics; Receptors, Nicotinic - physiology; Renal function; Reperfusion; Reperfusion Injury - prevention & control; Rodents; Sepsis; Spinal cord; Surgery; Transplantation; Transplants & implants; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0000469

Kidney ischemia/reperfusion injury (I/R) is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.