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Upregulation of Nitric Oxide Synthase Activity by All-trans Retinoic Acid and 13-cis Retinoic Acid in Human Malignant Keratinocytes
Biomed Sci Letters 2019;25:196-200
Published online June 30, 2019;
© 2019 The Korean Society For Biomedical Laboratory Sciences.

Ki-Young Moon,*

BioMedicinal Chemistry Laboratory, Department of Clinical Pathology, Gwangju Health University, Gwangju 62287, Korea
Correspondence to: Ki-Young Moon. Department of Clinical Pathology, Gwangju Health University, Gwangju 62287, Korea.
Tel: +82-62-958-7621, Fax: +82-62-958-7526, e-mail:
Received May 22, 2019; Revised June 14, 2019; Accepted June 18, 2019.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Effect of retinoids, i.e., all-trans retinoic acid and 13-cis retinoic acid, on the activity of nitric oxide synthase (NOS) was evaluated in human malignant keratinocytes to examine the possible correlation of retinoids with NOS activities. All-trans retinoic acid and 13-cis retinoic acid did not alter the nitric oxide (NO) production. However, in the presence of lipopolysaccharide (LPS, 1 µg/mL), they significantly increased NO release in a dose-dependent manner until 48 h at concentrations of 50~100 µM. The degree of upregulation of NO by all-trans retinoic acid and 13-cis retinoic acid increased up to 35% and 37%, respectively, compared to that by the control, which demonstrated the upregulation of LPS-inducible nitric oxide synthase (iNOS)-dependent generation of NO as well as showing a crucial link between retinoids-induced activity and NOS. Findings of this study now suggest that the upregulation of LPS-iNOS activity may be associated with modulation of retinoids-induced control of cellular developmental processes, which may produce new therapeutics of retinoids in the complexity of how NO affects human keratinocytes.
Keywords : All-trans retinoic acid, 13-cis retinoic acid, Inducible nitric oxide synthase, Nitric oxide, Human malignant keratinocytes