Macrophage polarization induced by quinolone antibiotics at environmental residue level

Abstract

Widespread use of quinolone antibiotics leads to serious residues in the environment and toxicity effects. This paper studied the effects of three typical quinolone antibiotics ciprofloxacin, norfloxacin and pipemidic acid on the polarization of macrophages RAW264.7 cells. The experimental concentrations were 0.01, 0.1, 1, 10, 100 and 1000 μg/L according to the environmental residual level. By MTT assay, phagocytosis assay and migration assay, macrophages were found to exhibit hormesis effect of low dose promotion and high dose inhibition. The detection of macrophages surface markers showed that 0.1 μg/L antibiotics increased the secretion of pro-inflammatory cytokines and induced macrophages to be M1-type, and 1000 μg/L antibiotics significantly increased the secretion of anti-inflammatory cytokines and induced macrophages to be M2-type. In order to explore the relationship between low-dose excitatory effects and polarization, the mechanism of 0.1 μg/L antibiotics inducing macrophages to M1-type was further studied. Results showed that 0.1 μg/L quinolone antibiotics activated the key proteins in the PI3K/Akt, Notch1, JNK and JAK2/STAT3 signaling pathways to cause the secretion of pro-inflammatory cytokines and induce inflammation. In order to eliminate inflammation, macrophages number feedback increased, phagocytosis and migration function enhanced, showing hormesis effect. In vitro macrophages experiment confirmed that quinolone antibiotics with environmental residual concentration had immunotoxicity.

Keywords: Hormesis effect; Inflammation; Macrophages; Polarization typing; Quinolone antibiotics.