RRC ID 69604
Author Ikegaya S, Inai K, Iwasaki H, Naiki H, Ueda T.
Title Azithromycin reduces tumor necrosis factor-alpha production in lipopolysaccharide-stimulated THP-1 monocytic cells by modification of stress response and p38 MAPK pathway.
Journal J Chemother
Abstract Macrolide antibiotics are known to have a variety of immunomodulatory effects in addition to antimicrobial activity, but the mechanisms of immunomodulation are still unclear. We investigated in vitro the effect of azithromycin on tumor necrosis factor alpha (TNF-alpha) production in lipopolysaccharide (LPS)-stimulated THP-1 cells, a human monocytic cell line, and compared the results with those for other macrolides, minocycline and ofloxacin. In the presence of LPS, treatment with azithromycin (AZM) resulted in a significant decrease in LPS-induced TNF-alpha production compared to that with other antimicrobial agents. the results of phosphorylation of three MAPKs, ERK, JNK and p38, indicated that the phospho-p38 level was reduced by AZM. Ikappab-alpha, an inhibitor of NFkappab, was not disrupted by the antibiotics. LPS-induced TNF-alpha release from THP-1 cells was inhibited in the presence of KNK437, a potent 70-kDa heat shock protein (HSP-70) inhibitor. Interestingly, the induction of HSP-70 by LPS was attenuated with the concurrent addition of AZM in the cells. AZM was found to restrain TNF-alpha production by monocytes at least in part by modifying the HSp-70 and p38 related signaling pathways to LPS stimulation.
Volume 21(4)
Pages 396-402
Published 2009-8-1
DOI 10.1179/joc.2009.21.4.396
PMID 19622457
MeSH Anti-Bacterial Agents / pharmacology* Azithromycin / pharmacology* Blotting, Western Cells, Cultured HSP70 Heat-Shock Proteins / metabolism Humans I-kappa B Proteins / metabolism Lipopolysaccharides / pharmacology* Monocytes / drug effects* Monocytes / metabolism NF-KappaB Inhibitor alpha Signal Transduction Tumor Necrosis Factor-alpha / metabolism* p38 Mitogen-Activated Protein Kinases / metabolism*
IF 1.661
Human and Animal Cells THP-1(RCB1189)