title: α7 Nicotinic acetylcholine receptor-specific antibody stimulates interleukin-6 production in human astrocytes through p38-dependent pathway.
abstract: α7 Nicotinic acetylcholine receptors (α7 nAChRs) are involved in regulating inflammatory cytokine production in macrophages and astrocytes. In the present paper, it is shown that α7-specific agonists PNU282987 (130nM) or choline (1.6mM) attenuated the interleukin-6 (IL-6) production stimulated by bacterial lipopolysaccharide in monocyte-derived U937 and astrocyte-derived U373 cell lines. In contrast, α7(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) α7(179-190)-specific antibody selected from the gene library of healthy human subject. The data obtained allow suggesting that α7-specific antibody can provoke neuroinflammation within the brain by inducing IL-6 production in astrocytes.
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine.
authors.forename: Olena
authors.initials: O
authors.lastname: Kalashnyk
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine.
authors.forename: Olena
authors.initials: O
authors.lastname: Lykhmus
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine.
authors.forename: Olena
authors.initials: O
authors.lastname: Oliinyk
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine.
authors.forename: Sergiy
authors.initials: S
authors.lastname: Komisarenko
authors.affiliation: Palladin Institute of Biochemistry, Kyiv, Ukraine. Electronic address: skok@biochem.kiev.ua.
authors.forename: Maryna
authors.initials: M
authors.lastname: Skok
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000737:chemistry / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D021122:Protein Subunits; D064569:alpha7 Nicotinic Acetylcholine Receptor; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Antibodies; Astrocytes; Inflammation; Interleukin-6; scFv antibodies; α7 Nicotinic acetylcholine receptor