Journal of Experimental Pharmacology
https://www.dovepress.com/getfile.php?fileID=5437
Functional role of the nicotinic arm of the acetylcholine regulatory axis in human B-cell lines
Juan Arredondo1 Denys Omelchenko2 Alexander I Chernyavsky1 Jing Qian1
Maryna Skok2 Sergei A Grando1
1Institute for Immunology and Departments of Dermatology and Biological Chemistry, University of California, Irvine, CA, USA;
2Palladin Institute of Biochemistry, Kiev, Ukraine
Abstract: We studied the involvement of nicotinic acetylcholine receptors (nAChRs) in the
inflammation-related activity of human B-cell lines. Activation of nAChRs in Daudi cells with
epibatidine abolished the pansorbin-dependent upregulation of the pro-inflammatory marker
Cox-2 both at the mRNA and protein levels, indicating that the nicotinergic signaling suppresses
B-cell activation. While the anti-inflammatory action on B-cells was mediated predominantly
through α7 nAChR, as could be judged from abolishing epibatidine effects with methyllycaconitine,
both α7 and non-α7 nAChRs, such as α2-containing receptors, were involved in regulation of B-cell apoptosis.
The net effect was antiapoptotic. To determine the role of nAChRs
in regulating B-cell activation/plasmacytic differentiation, we measured changes in the CD38,
CD138 and Bcl-6 gene expression. Epibatidine significantly (P 0.05) upregulated CD38 at the
transcriptional level and CD138 and Bcl-6 – at the translational levels. AR-R17779 significantly
(P 0.05) increased the protein levels of CD38 and CD138. In both cases, the effect of epibatidine
was abolished with Mec, and that of AR-R17779 – by MLA, demonstrating a functional
role of nAChRs in regulating Daudi cell differentiation. The obtained results revealed distinct
contributions of α7 and non-α7 nAChRs to regulation of B-cell activation/differentiation, and
suggested that signaling through the nicotinic arm of acetylcholine regulatory axis is important
for B-cell involvement in inflammation.