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.

Highlights

  • Acne vulgaris is one of the most common skin diseases in adolescents and young adults, and an estimated up to 80% of the population is affected by the condition at some point in their lives [1]

  • The production of IL-6 and IL-8 in HEKa cells was increased after exposure to heat-killed C. acnes concentration dependently

  • The effects of antimicrobial agents on proinflammatory cytokine production in HEKa cells were evaluated after exposure to 500 μg of the bacteria per ml (~1 × 109 CFU ml−1)

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Summary

Introduction

Acne vulgaris is one of the most common skin diseases in adolescents and young adults, and an estimated up to 80% of the population is affected by the condition at some point in their lives [1]. Many factors, such as increase or change of sebum composition, hormone

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