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

Int Immunopharmacol. 2014 Dec;23(2):475-9. doi: 10.1016/j.intimp.2014.09.022. Epub 2014 Oct 1.

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.

Keywords: Antibodies; Astrocytes; Inflammation; Interleukin-6; scFv antibodies; α7 Nicotinic acetylcholine receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Astrocytes / drug effects*
  • Astrocytes / metabolism
  • Cell Line
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Protein Subunits
  • alpha7 Nicotinic Acetylcholine Receptor / chemistry
  • alpha7 Nicotinic Acetylcholine Receptor / immunology*
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antibodies, Monoclonal
  • Interleukin-6
  • Protein Subunits
  • alpha7 Nicotinic Acetylcholine Receptor
  • p38 Mitogen-Activated Protein Kinases