Functional role of the nicotinic arm of the acetylcholine regulatory axis in human B-cell lines

Original Research

(1777) Views  (697) Full article downloads

Authors: Juan Arredondo, Denys Omelchenko, Alexander I Chernyavsky, et al

Published Date November 2009 Volume 2009:1(Default) Pages 1 - 7

DOI: http://dx.doi.org/10.2147/JEP.S7055

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.

Keywords: Daudi B cell line, nicotinic acetylcholine receptor, inflammation, apoptosis, pansorbin