title: Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.
abstract: 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.
authors.affiliation: Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Claude
authors.initials: C
authors.lastname: Sadis
authors.forename: Gwen
authors.initials: G
authors.lastname: Teske
authors.forename: Geurt
authors.initials: G
authors.lastname: Stokman
authors.forename: Carole
authors.initials: C
authors.lastname: Kubjak
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.forename: Fabrice
authors.initials: F
authors.lastname: Moore
authors.forename: Patrizia
authors.initials: P
authors.lastname: Loi
authors.forename: Bilo
authors.initials: B
authors.lastname: Diallo
authors.forename: Luc
authors.initials: L
authors.lastname: Barvais
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D006863:Hydrogen-Ion Concentration; D018836:Inflammation Mediators / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D015427:Reperfusion Injury / Q000517:prevention & control*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D018836:Inflammation Mediators; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine