title: Effect of azithromycin on Prevotella intermedia lipopolysaccharide-induced production of interleukin-6 in murine macrophages.
abstract: 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 JNK and p38 was not affected by azithromycin treatment. Azithromycin failed to prevent P. intermedia LPS from degrading IκB-α. Instead, azithromycin significantly diminished nuclear translocation and DNA binding activity of NF-κB 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-κB, 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.
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, 140 Baegyang-daero, 700beon-gil, Sasang-gu, Busan 617-736, Republic of Korea.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Choi
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, 140 Baegyang-daero, 700beon-gil, Sasang-gu, Busan 617-736, Republic of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jin
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea; Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Gyeongsangnam-do, Republic of Korea.
authors.forename: Jeom-Il
authors.initials: JI
authors.lastname: Choi
authors.affiliation: Department of Biological Science, College of Medical and Life Sciences, Silla University, 140 Baegyang-daero, 700beon-gil, Sasang-gu, Busan 617-736, Republic of Korea. Electronic address: ischoi@silla.ac.kr.
authors.forename: In Soon
authors.initials: IS
authors.lastname: Choi
authors.affiliation: Department of Periodontology, School of Dentistry, Pusan National University, 49 Busandaehak-ro, Mulgeum-eup, Yangsan, Gyeongsangnam-do 626-870, Republic of Korea; Dental Research Institute, Pusan National University Dental Hospital, Yangsan, Gyeongsangnam-do, Republic of Korea; Institute of Translational Dental Sciences, Pusan National University, Yangsan, Gyeongsangnam-do, Republic of Korea. Electronic address: sungjokim@pusan.ac.kr.
authors.forename: Sung-Jo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D018713:Prevotella intermedia; D016896:Treatment Outcome; D000093242:Interleukin-6 Inhibitors
chemical_list: D000900:Anti-Bacterial Agents; D017963:Azithromycin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000093242:Interleukin-6 Inhibitors; C577686:interleukin-6, mouse
keywords: Azithromycin; Interleukin-6; Lipopolysaccharide; NF-κB; SOCS1; STAT