Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages

被引:17
作者
Choi, Eun-Young [1 ]
Jin, Ji-Young [1 ]
Choi, Jeom-Il [2 ,3 ]
Choi, In Soon [1 ]
Kim, Sung-Jo [2 ,3 ,4 ]
机构
[1] Silla Univ, Coll Med & Life Sci, Dept Biol Sci, Pusan 617736, South Korea
[2] Pusan Natl Univ, Sch Dent, Dept Periodontol, Yangsan 626870, Gyeongsangnam D, South Korea
[3] Pusan Natl Univ, Dent Hosp, Dent Res Inst, Yangsan 626870, Gyeongsangnam D, South Korea
[4] Pusan Natl Univ, Inst Translat Dent Sci, Yangsan 626870, Gyeongsangnam D, South Korea
关键词
Azithromycin; Lipopolysaccharide; Interleukin-6; NF-kappa B; STAT; SOCS1; NF-KAPPA-B; GINGIVAL CREVICULAR FLUID; CYTOKINE SIGNALING SOCS; NITRIC-OXIDE; FACTOR-ALPHA; PERIODONTAL TREATMENT; EXPRESSION; SUPPRESSORS; MACROLIDE; PHOSPHORYLATION;
D O I
10.1016/j.ejphar.2014.02.008
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Interleukin-6 (IL-6) is a key proinflammatory cytokine which plays a central role in the pathogenesis of periodontal disease. Host modulatory agents targeting at inhibiting IL-6, therefore, appear to be beneficial in slowing the progression of periodontal disease and potentially reducing destructive aspects of the host response. The present study was designed to investigate the effect of the macrolide antibiotic azithromycin on IL-6 generation in murine macrophages treated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen implicated in inflammatory periodontal disease, and its mechanisms of action. Azithromycin significantly suppressed IL-6 production as well as its mRNA expression in P. intermedia LPS-activated RAW264.7 cells. LPS-induced activation of INK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading I kappa B-alpha. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-kappa B p50 subunit induced with LPS. Azithromycin inhibited P. intermedia LPS-induced STAT1 and STAT3 phosphorylation. In addition, azithromycin up-regulated the mRNA level of SOCS1 in cells treated with LPS. In conclusion, azithromycin significantly attenuated P. intermedia LPS-induced production of IL-6 in murine macrophages via inhibition of NF-kappa B, STAT1 and STAT3 activation, which is possibly related to the activation of SOCS1 signaling. Further in vivo studies are required to better evaluate the potential of azithromycin in the treatment of periodontal disease. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:10 / 16
页数:7
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