New Dihydropyridine Derivative Attenuates NF-κB Activation via Suppression of Calcium Influx in a Mouse BV-2 Microglial Cell Line

New Dihydropyridine Derivative Attenuates NF-κB Activation via Suppression of Calcium Influx in a Mouse BV-2 Microglial Cell Line

Kota Sato,^1,2 Yuto Sasaki,¹ Michiko Ohno-Oishi,¹ Kuniyuki Kano,³ Junken Aoki,³ Kosuke Ohsawa,³ Takayuki Doi,³ Hiroyuki Yamakoshi,³ Yoshiharu Iwabuchi,³ Chihiro Kawano,¹ Yoshiyuki Hirata⁴ and Toru Nakazawa^1,2,5,6

¹Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
²Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
³Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan
⁴Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
⁵Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Miyagi, Japan
⁶Department of Ophthalmic Imaging and Information Analytics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Activated microglia contribute to many neuroinflammatory diseases in the central nervous system. In this study, we attempted to identify an anti-inflammatory compound that could suppress microglial activation. We performed high-throughput screening with a chemical library developed at our institute. We performed a luciferase assay of nuclear factor-kappa B (NF-κB) reporter stable HT22 cells and identified a compound that was confirmed to inhibit the anti-inflammatory response in BV2 microglial cells. The selected dihydropyridine derivative can suppress the expression response of interleukin-1β (IL-1 β), interleukin-6 (IL-6), and tumor necrosis factor (TNF), as well as NF-κB phosphorylation and nuclear translocation, and reduce the intracellular calcium level. Thus, our identified compound has a potential role in suppressing microglial activation and may contribute to the development of a new therapeutic molecule against neuroinflammatory diseases.

Key words —— dihydropyridine derivative; drug screening; inflammation; microglia

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Tohoku J. Exp. Med., 2024 June, 263(2), 151-160.

*Present address: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

Correspondence: Toru Nakazawa, Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

e-mail: ntoru@oph.med.tohoku.ac.jp