Biphasic regulation of levofloxacin on lipopolysaccharide-induced IL-1beta production.
Fluoroquinolones have been known to exert modulatory activity on immune responses to microbial infection. However, the mechanism of this immunomodulation has not been well elucidated. In this study, we investigated the effect of levofloxacin on lipopolysaccharide (LPS)-induced production of interleukin-1beta (IL-1beta) in RAW264.7 cells. We showed that LPS-stimulated release of pre-synthesized IL-1beta was promoted by levofloxacin, in part via the p38 mitogen-activated protein kinase (MAPK) pathway. On the other hand, newly synthesized IL-1beta production was inhibited by levofloxacin. This immunoregulatory function of levofloxacin in the later phase as well as promotion of pre-synthesized IL-1beta release by levofloxacin in the early phase might be advantageous in the host defense to microbial pathogens.
Kitazawa
Takatoshi
T
Department of Infectious Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Nakayama
Kuniko
K
Okugawa
Shu
S
Koike
Kazuhiko
K
Shibasaki
Yoshikazu
Y
Ota
Yasuo
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D064704:Levofloxacin; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D015242:Ofloxacin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D007155:Immunologic Factors; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D064704:Levofloxacin; D015242:Ofloxacin