Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by human monocytes through AP-1 and NF-kappaB transcription factors

Abstract

Erythromycin and other macrolides are effective for the treatment of chronic inflammatory airway diseases such as diffuse panbronchiolitis (DPB) and chronic sinusitis. The effect of macrolides in DPB is suggested to be anti-inflammatory rather than antibacterial. We investigated the effects of clarithromycin on interleukin-8 (IL-8) production using human peripheral monocytes and the human monocytic leukaemia cell line, THP-1. Bacterial extracts from Escherichia coli, Pseudomonas aeruginosa and Helicobacter pylori, as well as E. coli-derived lipopolysaccharide (LPS), induced IL-8 production. Clarithromycin suppressed this production in a dose-dependent manner in both monocytes and THP-1 cells (49.3-75.0% inhibition at 10 mg/L). A luciferase reporter gene assay with plasmids containing a serially deleted IL-8 promoter fragment showed that both the activator protein-1 (AP-1) and/or the nuclear factor-kappa B (NF-kapp aB) binding sequences were responsible for the LPS and clarithromycin responsiveness of the IL-8 promoter. Consistently, in an electromobility shift assay, LPS increased the specific binding of both AP-1 and NF-kappaB, whereas clarithromycin suppressed it. Moreover, LPS and clarithromycin regulated three other promoters that have either the NF-kappa B or the AP-1 binding sequences: two synthetic (pAP-1-Luc and pNF-kappa B-Luc) and one naturally occurring (ELAM-Luc). Our results indicate that clarithromycin modified inflammation by sup-pressing IL-8 production and that clarithromycin may affect the expression of other genes through AP-1 and NF-kappa B. In addition to treatment of airway diseases, the anti-inflammatory effect of macrolides may be beneficial for the treatment of other inflammatory diseases such as chronic gastritis caused by H. pylori.

Tilmicosin-induced bovine neutrophil apoptosis is cell-specific and downregulates spontaneous LTB4 synthesis without increasing Fas expression

“…However, only recently have investigators begun to elucidate the mechanisms by which such antibiotics counteract inflammation. These mechanisms may include the reduction of PMN and mononuclear leukocyte infiltration [25,31], the inhibition of pro-inflammatory cytokine expression in PMN, monocytes, and epithelial cells [24,27,32,44], the inhibition of PMN adhesion to epithelial cells [24,26], and the suppression of the PMN oxidative burst [15,32,45]. In addition, recent studies have demonstrated the ability of several macrolides and azalides, including erythromycin and azithromycin, to induce PMN apoptosis in vitro [7,16,20,28].…”

Efektivitas Pemberian Antibiotik Disertai Lansoprazol pada Refluks Laringofaring dengan Infeksi Helicobacter pylori

“…Beberapa penelitian menunjukkan bahwa tingkat eradikasi H. pylori lebih costeffective dibandingkan dengan terapi PPI ataupun H2-antagonis jangka panjang. 11,12 Pada saat penilaian dengan menggunakan endoskopi ditemukan juga kelainan pada tonsila lingualis berupa hipertrofi dan rinosinusitis. Juga didapatkan hipertrofi dan edema pada mukosa hidung dan sinus paranasal, disertai keluarnya sekret purulen yang persisten dan efusi sinus.…”

Effect of Macrolide Antibiotics on Biological Activities Induced by Clostridium perfringens Alpha-Toxin

“…Macrolides, particularly those derived from 14-and 15-membered rings, exert antiinfammatory effects through a variety of signaling pathways including activator protein-1 (AP-1) and nuclear factor-kappaB (NF-κB) (Sato et al 1998, Khan et al 1999, Desaki et al 2000, Rubin and Tamaoki 2000, Kikuchi et al 2002. The antibiotics have been reported to impair the production of pro-inflammatory cytokines (Kadota et al 1993, Fujii et al 1995.…”