α7 Nicotinic acetylcholine receptor agonistinhibits bone cement particles stimulated secretion of inflammatory cytokinesin peripheral blood monocytes of mice / 基础医学与临床

ABSTRACT

Objective To investigate the effect of α7 nicotinic acetylcholine receptor(α7nAChR) agonist agent PNU282987 on bone cement particles stimulated secretion of inflammatory cytokines in peripheral blood monocytes and its molecular mechanism.Methods Mouse peripheral blood monocytes were isolated and the inflammatory response were induced by PMMA particles.TNF-α, IL-1β and IL-6 concentration in culture supernatant were measured by ELISA.TNF-α, IL-1β and IL-6 mRNA expression were measured by RT-PCR.p-p65, p65, p-JAK2, JAK2, p-STAT3, STAT3, and β-actin expression were detected by Western blot.NF-κB DNA binding activity were measured by ELISA.ResultsAfter stimulation of PMMA particles, TNF-α, IL-1β and IL-6 concentration in culture supernatant was significantly increased(P<0.05), TNF-α, IL-1β and IL-6 mRNA expression was significantly increased (P<0.05), p-p65, p-JAK2 and p-STAT3 expression and NF-κB DNA binding activity was also increased significantly (P<0.05).However, after PNU282987 treatment, TNF-α, IL-1β and IL-6 concentration in culture supernatant decreased(P<0.05), TNF-α, IL-1β and IL-6 mRNA expression decreased in a concentration gradient way(P<0.05), p-p65, p-JAK2 and p-STAT3expression and NF-κB p65 DNA binding activity was also decreased(P<0.05).Conclusions α7nAChR agonist PNU282987 significantly inhibites PMMA bone cement particles induced secretion of inflammatory cytokines in peripheral blood monocytes of mice.