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Dehydroxymethylepoxyquinomicin, a novel nuclear factor–κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1β in human corneal fibroblasts

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Abstract

Purpose

Dehydroxymethylepoxyquinomicin (DHMEQ) is derived from the antibiotic, epoxyquinomicin C, and is a novel low molecular weight nuclear factor-κB (NF-κB) inhibitor. We investigated the effects of DHMEQ on the expression of chemokines and the intercellular adhesion molecule (ICAM)-1 induced by proinflammatory cytokines in cultures of the human corneal fibroblasts (HCFs).

Methods

The cytotoxicity of DHMEQ on cultured HCFs was evaluated by cell proliferation assays. Cultures were exposed to interleukin (IL)-1β, and the production of IL-8 and monocyte chemoattractant protein (MCP)-1 was assessed by enzyme-linked immunosorbent assay. The degree of expression of ICAM-1 was measured by flow cytometry. The translocation of NF-κB p65 into the nucleus of HCFs was assessed by immunocytochemistry.

Results

DHMEQ was not toxic to cultured HCFs at doses up to 10 μg/ml. DHMEQ significantly suppressed the production of both IL-8 and MCP-1 in IL-1β-stimulated HCFs. In addition, DHMEQ down-regulated ICAM-1 expression in IL-1β-stimulated HCFs in a dose-dependent manner. DHMEQ inhibited the IL-1β-induced nuclear accumulation of p65, a component of NF-κB, in HCFs.

Conclusions

The suppression of inflammatory chemokines IL-8 and MCP-1 and inhibition of the expression of ICAM-1 in cultured HCFs by DHMEQ indicates that DHMEQ may have a therapeutic potential for treating ICAM-1 and chemokine-mediated corneal inflammatory disorders.

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Acknowledgments

We thank Ms. Nobuko Takahashi for her technical assistance and Professor Emeritus Duco Hamasaki of Bascom Palmer Eye Institute of the University of Miami for English editing.

Conflict of interest

This work was supported by Grant for Scientific Research from Kyorin University, Tokyo, Japan.

Commercial relationships: none

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan

    Sosuke Inokawa, Takayo Watanabe, Hiroshi Keino, Akito Hirakata & Annabelle A. Okada

  2. Department of Ophthalmology, Hiroshima University School of Medicine, Hiroshima, Japan

    Sosuke Inokawa

  3. Division of Radioisotope Research, Kyorin University School of Medicine, Tokyo, Japan

    Yasuhiko Sato

  4. Department of Ophthalmology, Kochi Medical School, Kochi, Japan

    Ken Fukuda & Atsuki Fukushima

  5. Department of Molecular Target Medicine Screening, Aichi Medical University, Nagakute, Japan

    Kazuo Umezawa

Authors
  1. Sosuke Inokawa
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  2. Takayo Watanabe
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  3. Hiroshi Keino
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  4. Yasuhiko Sato
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  9. Kazuo Umezawa
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Correspondence to Hiroshi Keino.

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Inokawa, S., Watanabe, T., Keino, H. et al. Dehydroxymethylepoxyquinomicin, a novel nuclear factor–κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1β in human corneal fibroblasts. Graefes Arch Clin Exp Ophthalmol 253, 557–563 (2015). https://doi.org/10.1007/s00417-014-2879-9

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  • DOI: https://doi.org/10.1007/s00417-014-2879-9

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