title: Monocytes primed with GTS-21/α7 nAChR (nicotinic acetylcholine receptor) agonist develop anti-inflammatory memory.
abstract: BACKGROUND
  The neural system can finely tune immune system, especially pro- or anti-inflammatory responses of monocytes/macrophages. To maintain immune homeostasis, monocytes/macrophages are supposed to be primed by α7 nAChR agonist to establish anti-inflammatory memory.
  
  
  OBJECTIVE
  To study whether activation of α7 nAChR would elicit anti-inflammatory memory in splenic monocytes in vivo and J774 monocytes in vitro .
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  The wildtype mice were sacrificed 4 or 12 h after receiving intravenous injection of GTS-21. The splenocytes were isolated and stimulated with LPS for 4 h to detect Ly6C hi TNF-α +  monocytes by flow cytometry. In the in vitro study, J774 monocytes received priming with GTS-21, washing GTS-21 out and resting, and thereafter stimulating with TLR ligands. The TNF-α protein and Tnfα , Il1β and il6 mRNAs were measured to evaluate anti-inflammatory responses. The H3K9ac, H4K5ac, H4K8ac, Acetyl-CBP, CBP (CREB-binding protein), PCAF (P300/CBP-associated factor) and Acetyl-NF-kB levels were measured in GTS-21-primed monocytes.
  
  
  RESULTS
  Activation of α7 nAChR by GTS-21 suppressed TNF-α production in splenic Ly6C hi monocytes. In vivo -GTS-21-primed splenic Ly6C hi monocytes passed on anti-inflammatory feature if stimulated with LPS in vitro . J774 monocytes primed with GTS-21 developed anti-inflammatory trait in response to LPS (TLR4), Poly:IC (TLR3) and R848 (TLR7/8) ligands. In GTS-21-primed monocytes, H3K9ac, H4K5ac, H4K8ac, Acetyl-CBP, CBP, PCAF and Acetyl-NF-kB were reduced 4 h after washing and resting. In the nuclear extract, PCAF, Acetyl-NF-kB, p-NF-kB and p-STAT3 were decreased in LPS-stimulated GTS-21 primed J774 monocytes 4 h after washing and resting.
  
  
  CONCLUSIONS
  Monocytes primed by α7 nAChR agonist developed anti-inflammatory memory.
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, 200031.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, 200031.
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Unit of Pathogen-host Interaction and Epigenetics, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Unit of Pathogen-host Interaction and Epigenetics, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031.
authors.forename: L
authors.initials: L
authors.lastname: Jiang
authors.affiliation: CAS Key Laboratory of Molecular Virology and Immunology, Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, University of Chinese Academy of Sciences, 200031.
authors.forename: Xiao
authors.initials: X
authors.lastname: Su
mesh_terms: D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
chemical_list: D001597:Benzylidene Compounds; D016207:Cytokines; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D011725:Pyridines; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D050882:CREB-Binding Protein