Journal of Antimicrobial Chemotherapy (2002) 49, 745-755
© 2002 The British Society for Antimicrobial Chemotherapy
Clarithromycin suppresses lipopolysaccharide-induced interleukin-8 production by human monocytes through AP-1 and NF-
B transcription factors
1Department of Respiratory Oncology and Molecular Medicine, Division of Cancer Control, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575; 2Sendai Kousei Hospital, 4-15 Hirose-chou, Aoba-ku, Sendai 980-0873, Japan
Received 12 October 2001; returned 25 November 2001; revised 2 January 2002; accepted 24 January 2002.
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-
B (NF-B) 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-B, whereas clarithromycin suppressed it. Moreover, LPS and clarithromycin regulated three other promoters that have either the NF-B or the AP-1 binding sequences: two synthetic (pAP-1-Luc and pNF-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-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.
* Corresponding author. Tel: +81-22-717-8539; Fax: +81-22-717-8549; E-mail: hagiwark{at}idac.tohoku.ac.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. S. Khalifeh, M. M. Amawi, E. A. Abu-Basha, and I. B. Yonis Assessment of humoral and cellular-mediated immune response in chickens treated with tilmicosin, florfenicol, or enrofloxacin at the time of Newcastle disease vaccination Poult. Sci., October 1, 2009; 88(10): 2118 - 2124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakanishi, D. Kobayashi, Y. Asano, T. Sakurai, M. Kashimura, S. Okuyama, Y. Yoneda, S. D. Shapiro, and K. Takayama Clarithromycin Prevents Smoke-induced Emphysema in Mice Am. J. Respir. Crit. Care Med., February 15, 2009; 179(4): 271 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chmura, X. Bai, M. Nakamura, P. Kandasamy, M. McGibney, K. Kuronuma, H. Mitsuzawa, D. R. Voelker, and E. D. Chan Induction of IL-8 by Mycoplasma pneumoniae membrane in BEAS-2B cells Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L220 - L230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ogawa, J.-i. Suzuki, K. Hishikari, K. Takayama, H. Tanaka, and M. Isobe Clarithromycin Attenuates Acute and Chronic Rejection Via Matrix Metalloproteinase Suppression in Murine Cardiac Transplantation J. Am. Coll. Cardiol., May 20, 2008; 51(20): 1977 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Simpson, H. Powell, M. J. Boyle, R. J. Scott, and P. G. Gibson Clarithromycin Targets Neutrophilic Airway Inflammation in Refractory Asthma Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 148 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-C. Chow, S. Yang, C.-J. Huang, C.-Y. Tzen, Y.-H. Su, and P. S. Wang Prophylactic Intravesical Instillation of Epinephrine Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats Experimental Biology and Medicine, April 1, 2007; 232(4): 565 - 570. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Lotter, K. Hocherl, M. Bucher, and F. Kees In vivo efficacy of telithromycin on cytokine and nitric oxide formation in lipopolysaccharide-induced acute systemic inflammation in mice J. Antimicrob. Chemother., September 1, 2006; 58(3): 615 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Giamarellos-Bourboulis, V. Tziortzioti, P. Koutoukas, F. Baziaka, M. Raftogiannis, A. Antonopoulou, T. Adamis, L. Sabracos, and H. Giamarellou Clarithromycin is an effective immunomodulator in experimental pyelonephritis caused by pan-resistant Klebsiella pneumoniae J. Antimicrob. Chemother., May 1, 2006; 57(5): 937 - 944. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Kwakkel, W M Wiersinga, and A Boelen Differential involvement of nuclear factor-{kappa}B and activator protein-1 pathways in the interleukin-1{beta}-mediated decrease of deiodinase type 1 and thyroid hormone receptor {beta}1 mRNA. J. Endocrinol., April 1, 2006; 189(1): 37 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shinkai, G. H. Foster, and B. K. Rubin Macrolide antibiotics modulate ERK phosphorylation and IL-8 and GM-CSF production by human bronchial epithelial cells Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L75 - L85. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Beringer, K. M. T. Huynh, J. Kriengkauykiat, L. Bi, N. Hoem, S. Louie, E. Han, T. Nguyen, D. Hsu, P. A. Rao, et al. Absolute Bioavailability and Intracellular Pharmacokinetics of Azithromycin in Patients with Cystic Fibrosis Antimicrob. Agents Chemother., December 1, 2005; 49(12): 5013 - 5017. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Williams, H. F. Galley, A. M. Watt, and N. R. Webster Differential effects of three antibiotics on T helper cell cytokine expression J. Antimicrob. Chemother., September 1, 2005; 56(3): 502 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Barnes and R. A. Stockley COPD: current therapeutic interventions and future approaches Eur. Respir. J., June 1, 2005; 25(6): 1084 - 1106. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Imamura, K. Yanagihara, Y. Mizuta, M. Seki, H. Ohno, Y. Higashiyama, Y. Miyazaki, K. Tsukamoto, Y. Hirakata, K. Tomono, et al. Azithromycin Inhibits MUC5AC Production Induced by the Pseudomonas aeruginosa Autoinducer N-(3-Oxododecanoyl) Homoserine Lactone in NCI-H292 Cells Antimicrob. Agents Chemother., September 1, 2004; 48(9): 3457 - 3461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yamasawa, K. Oshikawa, S. Ohno, and Y. Sugiyama Macrolides Inhibit Epithelial Cell-Mediated Neutrophil Survival by Modulating Granulocyte Macrophage Colony-Stimulating Factor Release Am. J. Respir. Cell Mol. Biol., April 1, 2004; 30(4): 569 - 575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Giamarellos-Bourboulis, T. Adamis, G. Laoutaris, L. Sabracos, V. Koussoulas, M. Mouktaroudi, D. Perrea, P. E. Karayannacos, and H. Giamarellou Immunomodulatory Clarithromycin Treatment of Experimental Sepsis and Acute Pyelonephritis Caused by Multidrug-Resistant Pseudomonas aeruginosa Antimicrob. Agents Chemother., January 1, 2004; 48(1): 93 - 99. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-H. Choi, M.-J. Song, S.-H. Kim, S.-M. Choi, D.-G. Lee, J.-H. Yoo, and W.-S. Shin Effect of Moxifloxacin on Production of Proinflammatory Cytokines from Human Peripheral Blood Mononuclear Cells Antimicrob. Agents Chemother., December 1, 2003; 47(12): 3704 - 3707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shimizu, S. Shimizu, R. Hattori, E. C. Gabazza, and Y. Majima In Vivo and In Vitro Effects of Macrolide Antibiotics on Mucus Secretion in Airway Epithelial Cells Am. J. Respir. Crit. Care Med., September 1, 2003; 168(5): 581 - 587. [Abstract] [Full Text] [PDF]
|
|