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.
Highlights
Cells of the monocytic lineage, including monocytes, macrophages and dendritic cells, are vital for the immune response and are involved in a multitude of inflammatory disorders [1,2,3].PLOS ONE | DOI:10.1371/journal.pone.0150230 February 29, 2016nicotinic acetylcholine receptor (nAChR) Modulate classically-activated monocytes/macrophages (M1) Monocyte Production
It has previously been shown that binding sites for homomeric (α7, α9) and heteromeric (i.e. β2-containing) nAChR ligands are present in mouse bone marrow cell (BMC), and that nAChR expression may be modulated throughout immune cell development [27,28]
We found that nAChR mRNA expression in BMCs is highly heterogeneous and
Summary
The goal of the present study was to determine if nicotine modulates the production of bone marrow -derived monocytes/macrophages
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