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Azithromycin suppresses Th1- and Th2-related chemokines IP-10/MDC in human monocytic cell line.

Research paper by Chang-Hung CH Kuo, Min-Sheng MS Lee, Hsuan-Fu HF Kuo, Yi-Ching YC Lin, Chih-Hsing CH Hung

Indexed on: 26 Nov '19Published on: 25 Nov '19Published in: Journal of Microbiology, Immunology and Infection



Abstract

Cytokines and chemokines play critical roles in the pathogenesis of asthma. Azithromycin, a macrolides, is frequently used in asthmatic children with lower respiratory tract infection and is reported having anti-inflammatory and immunomodulatory effects. However, the effects of azithromycin on the expression of TNF-α, Th1- and Th2-related chemokines, and neutrophil chemoattractant are unknown. We investigated the in vitro effects of azithromycin on the expression of TNF-α, Th1-related chemokine interferon-γ-inducible protein-10 (IP-10/CXCL10), Th2-related chemokine macrophage-derived chemokine (MDC/CCL22) and neutrophil chemoattractant growth-related oncogene-α (GRO-α/CXCL1) in THP-1 cells as a model for human monocytes. THP-1 cells were pretreated with various concentrations of azithromycin before Toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) stimulation. TNF-α, IP-10, MDC and GRO-α were measured by ELISA. Intracellular signaling was investigated by pathway inhibitors and Western blot. Azithromycin suppressed MDC and IP-10 expression in LPS-stimulated THP-1 cells. However, azithromycin had no effect LPS-induced TNF-α and GRO-α expression. Western blotting revealed that azithromycin suppressed LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK)-JNK and ERK expression, and also suppressed LPS-induced phosphorylation of nuclear factor (NF) κB-p65 expression. Azithromycin suppressed LPS-induced MDC expression via the MAPK-JNK and the NFκB-p65 pathway. Azithromycin also suppressed LPS-induced IP-10 via the MAPK-JNK/ERK and the NFκB-p65 pathway. Azithromycin may benefit asthmatic patients by suppressing chemokines expression. Copyright © 2019. Published by Elsevier B.V.