title: Nicotinic receptor β2 determines NK cell-dependent metastasis in a murine model of metastatic lung cancer.
abstract: Cigarette smoke exposure markedly compromises the ability of the immune system to protect against invading pathogens and tumorigenesis. Nicotine is a psychoactive component of tobacco products that acts as does the natural neurotransmitter, acetylcholine, on nicotinic receptors (nAChRs). Here we demonstrate that natural killer (NK) cells strongly express nAChR β2. Nicotine exposure impairs the ability of NK cells to kill target cells and release cytokines, a process that is largely abrogated by nAChR β2 deficiency. Further, nicotinic suppression of NF-κB-induced transcriptional activity in NK cells is dependent on nAChR β2. This nAChR subtype also plays a large role in the NK cell-mediated control of melanoma lung metastasis, in a murine lung metastasis model exposed to nicotine. Our findings suggest nAChR β2 as a prominent pathway for nicotine induced impairment of NK cell functions which contributes to the occurrence of smoking-related pathologies.
authors.affiliation: Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China. jhao0216@gmail.com
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
authors.forename: Fu-Dong
authors.initials: FD
authors.lastname: Shi
authors.forename: Mohammed
authors.initials: M
authors.lastname: Abdelwahab
authors.forename: Samuel X
authors.initials: SX
authors.lastname: Shi
authors.forename: Alain
authors.initials: A
authors.lastname: Simard
authors.forename: Paul
authors.initials: P
authors.lastname: Whiteaker
authors.forename: Ronald
authors.initials: R
authors.lastname: Lukas
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D005260:Female; D007694:Killer Cells, Natural / Q000502:physiology*; D008175:Lung Neoplasms / Q000473:pathology*; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D009538:Nicotine; D011978:Receptors, Nicotinic