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KMID : 0606920100180010071
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Biomolecules & Therapeutics
2010 Volume.18 No. 1 p.71 ~ p.76
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Ethacrynic Acid and Citral Suppressed the All Trans Retinoid-Induced Monocyte Chemoattractant Protein-1 Production in Human Dermal Fibroblasts
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Kim Kwang-Mi
Noh Min-Soo
Kim Soo-Hyun
Park Mi-Kyung
Lee Hye-Ja
Kim Soo-Youl
Lee Chang-Hoon
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Abstract
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Skin irritation caused by retinol and retinoic acid results in mild erythema called as retinoid dermatitis. To develop compounds modulating the retinoid dermatitis, we tried to establish the screening method for retinoid dermatitis. At first we examined the inflammatory cytokine profile in neonatal human dermal fibroblasts which are known to be one of main site of retinoid action. As a result, interleukin-8 (IL-8) and monocytes chemoattractant protein-1 (MCP-1) were significantly produced by all trans retinoic acid (ATRA) and all trans retinol (ATROL) in dermal fibroblasts. Especially the production of MCP-1 was more than that of IL-8. The production of MCP-1 by retinoid was dose-dependently increased, continuing up to 24 hrs. After then using ethacrynic acid (ECA) known to reduce mouse ear edema induced by ATRA, we checked whether ECA suppressed the production of MCP-1. As a result, ECA effectively suppressed the production of MCP-1 in the ATRA- or ATROL-treated-fibroblasts. These results suggested that screening method effectively reflects the in vivo anti-inflammatory activity of ECA. It was reported that citral inhibited the enzyme involved in the conversion of ATROL to ATRA. We showed that citral suppressed the production of MCP-1 in ATROL-treated fibroblasts. We expect these finding might be helpful to find useful compounds modulating the side effects of retinoid or retinoid dermatitis.
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KEYWORD
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MCP-1, All trans retinoic acid, Dermal fibroblast, All trans retinol, Ethacrynic acid, Citral
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