-Original-

Anti-Inflammatory Effects of EM900 on Cultured Human Nasal Epithelial Cells

Nozomu Wakayama¹, Shoji Matsune¹, Eriko Takahara¹, Kuwon Sekine¹, Yuma Yoshioka¹, Mariko Ishida¹, Satoshi Yamaguchi¹, Kimihiro Okubo², Toshiaki Sunazuka³ and Satoshi Ōmura³

¹Department of Otolaryngology, Nippon Medical School Musashi Kosugi Hospital, Kanagawa, Japan
²Department of Otolaryngology, Nippon Medical School, Graduate School of Medicine, Head and Neck Surgery, Tokyo, Japan
³Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan

Objectives: Macrolide therapy is an important conservative therapy for chronic rhinosinusitis, especially in Japan. The mechanism underlying this therapy involves anti-inflammatory and not antimicrobial activity. However, the administration of long-term low-dose macrolides (LTLMs) causes an increase in the number of antibiotic-resistant bacteria. EM900 is a derivative of erythromycin (EM), with anti-inflammatory but not antibacterial effects. It does not induce macrolide-resistant bacteria as shown by LTLM. In the present study, we analyzed the inhibitory effects of EM900 in comparison with those of clarithromycin (CAM) on inflammatory cytokine production in human nasal epithelial cells (HNEpCs).
Methods: After HNEpCs were cultured for 4 days, CAM or EM900 was added into the culture, followed by stimulation with tumor necrosis factor (TNF)-α. Interleukin (IL)-8 and vascular endothelial growth factor (VEGF) levels were measured using real-time polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA).
Results: Both the ELISA and RT-PCR showed that EM900 and CAM significantly inhibited IL-8 production in HNEpCs. In contrast, EM900 and CAM did not suppress the increased VEGF production when HNEpCs were stimulated with TNF-α.
Conclusion: EM900 showed an anti-inflammatory effect, such as that of CAM, due to the inhibitory effect on IL-8 production in HNEpCs.

J Nippon Med Sch 2018; 85: 265-270

Keywords
chronic rhinosinusitis, macrolide, EM900, IL-8, TNF-α

Correspondence to
Nozomu Wakayama, MD, PhD, Department of Otolaryngology, Nippon Medical School Musashi Kosugi Hospital, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-8533, Japan
waka84@nms.ac.jp

Received, January 25, 2018
Accepted, May 27, 2018