title: Nicotinic Acetylcholine Receptors Modulate Bone Marrow-Derived Pro-Inflammatory Monocyte Production and Survival.
abstract: It is increasingly clear that nicotinic acetylcholine receptors (nAChRs) are involved in immune regulation, and that their activation can protect against inflammatory diseases. Previous data have shown that nicotine diminishes the numbers of peripheral monocytes and macrophages, especially those of the pro-inflammatory phenotype. The goal of the present study was to determine if nicotine modulates the production of bone marrow -derived monocytes/macrophages. In this study, we first found that murine bone marrow cells express multiple nAChR subunits, and that the α7 and α9 nAChRs most predominant subtypes found in immune cells and their precursors. Using primary cultures of murine bone marrow cells, we then determined the effect of nicotine on monocyte colony-stimulating factor and interferon gamma (IFNγ)-induced monocyte production. We found that nicotine lowered the overall number of monocytes, and more specifically, inhibited the IFNγ-induced increase in pro-inflammatory monocytes by reducing cell proliferation and viability. These data suggested that nicotine diminishes the ratio of pro-inflammatory versus anti-inflammatory monocyte produced in the bone marrow. We thus confirmed this hypothesis by measuring cytokine expression, where we found that nicotine inhibited the production of the pro-inflammatory cytokines TNFα, IL-1β and IL-12, while stimulating the secretion of IL-10, an anti-inflammatory cytokine. Finally, nicotine also reduced the number of pro-inflammatory monocytes in the bone marrow of LPS-challenged mice. Overall, our data demonstrate that both α7 and α9 nAChRs are involved in the regulation of pro-inflammatory M1 monocyte numbers.
authors.affiliation: Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: St-Pierre
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Roy
authors.affiliation: Centre de Formation Médicale du Nouveau-Brunswick, Moncton, NB, Canada.
authors.forename: Camille
authors.initials: C
authors.lastname: Champigny
authors.affiliation: Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, Canada.
authors.forename: Éric
authors.initials: É
authors.lastname: LeBlanc
authors.affiliation: Boys Town National Research Hospital, Omaha, NE, United States of America.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Morley
authors.affiliation: Department of Neurology and Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Hao
authors.affiliation: Département de Chimie et Biochimie, Université de Moncton, Moncton, NB, Canada.|Centre de Formation Médicale du Nouveau-Brunswick, Moncton, NB, Canada.
authors.forename: Alain R
authors.initials: AR
authors.lastname: Simard
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*
chemical_list: D003115:Colony-Stimulating Factors; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D016753:Interleukin-10; D009538:Nicotine; D007371:Interferon-gamma