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Graefe's Archive for Clinical and Experimental Ophthalmology

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01-04-2015 | Basic Science

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

Authors: Sosuke Inokawa, Takayo Watanabe, Hiroshi Keino, Yasuhiko Sato, Akito Hirakata, Annabelle A. Okada, Ken Fukuda, Atsuki Fukushima, Kazuo Umezawa

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 4/2015

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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Title: Dehydroxymethylepoxyquinomicin, a novel nuclear factor–κB inhibitor, reduces chemokines and adhesion molecule expression induced by IL-1β in human corneal fibroblasts
Authors: Sosuke Inokawa
Takayo Watanabe
Hiroshi Keino
Yasuhiko Sato
Akito Hirakata
Annabelle A. Okada
Ken Fukuda
Atsuki Fukushima
Kazuo Umezawa
Publication date: 01-04-2015
Publisher: Springer Berlin Heidelberg
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 4/2015
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-014-2879-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Purpose

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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