α7 Nicotinic acetylcholine receptor-specific antibody stimulates interleukin-6 production in human astrocytes through p38-dependent pathway

alpha 7 Nicotinic acetylcholine receptors (alpha 7 nAChRs) are involved in regulating inflammatory cytokine production in macrophages and astrocytes. In the present paper, it is shown that alpha 7-specific agonists PNU282987 (130 nM) or choline (1.6 mM) attenuated the interleukin-6 (IL-6) production stimulated by bacterial lipopolysaccharide in monocyte-derived U937 and astrocyte-derived U373 cell lines. In contrast, alpha 7(179-190)-specific antibody, which bound to and was internalized by U373 cells, stimulated IL-6 production in p38 kinase-dependent manner in the absence of lipopolysaccharide. The antibody effect was not due to its Fc-fragment because similar capacity was found for recombinant single-chain (scFv) alpha 7(179-190)-specific antibody selected from the gene library of healthy human subject. The data obtained allow suggesting that alpha 7-specific antibody can provoke neuroinflammation within the brain by inducing IL-6 production in astrocytes. (C) 2014 Elsevier B.V. All rights reserved.