Anti-inflammatory effects of ozenoxacin, a topical quinolone antimicrobial agent
Keisuke Tabara, Rie Tamura, Aki Nakamura, Sachi Mori, Takamichi Kitano, Koki Fujikawa, Mika Fujikawa, K. Okamoto, Shoji Kanayama, Hideya Uratsuji, Fumiaki Ikeda, Tatsumi Matsumoto
Abstract
Abstract Ozenoxacin is a topical quinolone showing potent antimicrobial activities against Gram-negative and Gram-positive bacteria and is widely used for the treatment of inflammatory acne. However, the anti-inflammatory activities of ozenoxacin have not been examined so far. In the present study, we investigated the in vitro and in vivo anti-inflammatory effects of ozenoxacin. The production of interleukin (IL)-6 and IL-8 by human epidermal keratinocytes stimulated by heat-killed Cutibacterium acnes was significantly inhibited by ozenoxacin at concentrations from 1 to 30 μg ml −1 . Likewise, the production of IL-6, IL-8, and tumor necrosis factor alpha by stimulated THP-1 cells, a human monocyte cell line, was inhibited by ozenoxacin at concentrations from 1 to 30 μg ml −1 . The production of IL-1β by THP-1 was also inhibited by ozenoxacin at the concentration of 30 μg ml −1 . Phosphorylation of the mitogen - activated protein kinases and degradation of IκB-α, an inhibitory factor of NF-κB in keratinocytes and THP-1 cells, was increased by stimulation with heat-killed C. acnes . Of these activated intracellular pathways, the p38 phosphorylation pathway was remarkably reduced by ozenoxacin in both keratinocytes and THP-1 cells. In addition, the application of 2% ozenoxacin suppressed the increase in the ear thickness of rats induced by an intracutaneous injection of heat-killed C. acnes . These findings suggest that ozenoxacin possesses an anti-inflammatory activity, which may contribute to its therapeutic effects on inflammatory acne.