1. Anti-inflammatory effects of ozenoxacin, a topical quinolone antimicrobial agent
- Author
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Kazuaki Okamoto, Mika Fujikawa, Shoji Kanayama, Koki Fujikawa, Takamichi Kitano, Fumiaki Ikeda, Rie Tamura, Keisuke Tabara, Tatsumi Matsumoto, Hideya Uratsuji, Sachi Mori, and Aki Nakamura
- Subjects
0301 basic medicine ,Male ,medicine.drug_class ,p38 mitogen-activated protein kinases ,030106 microbiology ,Anti-Inflammatory Agents ,Aminopyridines ,Pharmacology ,Inflammatory diseases ,Quinolones ,Anti-inflammatory ,Article ,Cell Line ,Rats, Sprague-Dawley ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,In vivo ,Drug Discovery ,Acne Vulgaris ,medicine ,Animals ,Humans ,Propionibacterium acnes ,Inflammation ,Dose-Response Relationship, Drug ,Chemistry ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Monocyte ,Interleukin-8 ,Interleukin ,In vitro ,Rats ,Disease Models, Animal ,medicine.anatomical_structure ,Ozenoxacin ,Tumor necrosis factor alpha - 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.
- Published
- 2020