当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > Azithromycin distinctively modulates classical activation of human monocytes in vitro.

Azithromycin distinctively modulates classical activation of human monocytes in vitro.

Abstract：

BACKGROUND AND PURPOSE:Azithromycin has been reported to modify activation of macrophages towards the M2 phenotype. Here, we have sought to identify the mechanisms underlying this modulatory effect of azithromycin on human monocytes, classically activated in vitro. EXPERIMENTAL APPROACH:Human blood monocytes were primed with IFN-γ for 24 h and activated with LPS for 24 h. Azithromycin, anti-inflammatory and lysosome-affecting agents were added 2 h before IFN-γ. Cytokine and chemokine expression was determined by quantitative PCR and protein release by ELISA. Signalling molecules were determined by Western blotting and transcription factor activation quantified with a DNA-binding ELISA kit. KEY RESULTS:Azithromycin (1.5-50 µM) dose-dependently inhibited gene expression and/or release of M1 macrophage markers (CCR7, CXCL 11 and IL-12p70), but enhanced CCL2, without altering TNF-α or IL-6. Azithromycin also enhanced the gene expression and/or release of M2 macrophage markers (IL-10 and CCL18), and the pan-monocyte marker CD163, but inhibited that of CCL22. The Toll-like receptor (TLR) 4 signalling pathway was modulated, down-regulating NF-κB and STAT1 transcription factors. The inhibitory profile of azithromycin differed from that of dexamethasone, the phosphodiesterase-4 inhibitor roflumilast and the p38 kinase inhibitor SB203580 but was similar to that of the lysosomotropic drug chloroquine. Effects of concanamycin and NH4Cl, which also act on lysosomes, differed significantly. CONCLUSIONS AND IMPLICATIONS:Azithromycin modulated classical activation of human monocytes by inhibition of TLR4-mediated signalling and possible effects on lysosomal function, and generated a mediator expression profile that differs from that of monocyte/macrophage phenotypes so far described.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Vrančić M,Banjanac M,Nujić K,Bosnar M,Murati T,Munić V,Stupin Polančec D,Belamarić D,Parnham MJ,Eraković Haber V

doi

10.1111/j.1476-5381.2011.01576.x

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

1348-60

issue

eissn

0007-1188

issn

1476-5381

journal_volume

165

pub_type

杂志文章

在线工具

Azithromycin distinctively modulates classical activation of human monocytes in vitro.