Monocytes primed with GTS-21/α7 nAChR (nicotinic acetylcholine receptor) agonist develop anti-inflammatory memory.

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Monocytes primed with GTS-21/α7 nAChR (nicotinic acetylcholine receptor) agonist develop anti-inflammatory memory.

QJM. 2017 Jan 12;:

Authors: Yang X, Zhao C, Chen X, Jiang L, Su X

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.
AIM: To study whether activation of α7 nAChR would elicit anti-inflammatory memory in splenic monocytes in vivo and J774 monocytes in vitro DESIGN: : 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, PCAF, 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.

PMID: 28082382 [PubMed - as supplied by publisher]

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