AUTHOR=Ko Yoo-Seung , Gi Eun-Ji , Lee Sungsu , Cho Hyong-Ho 

TITLE=Dual red and near-infrared light-emitting diode irradiation ameliorates LPS-induced otitis media in a rat model

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=11

YEAR=2023

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2023.1099574

DOI=10.3389/fbioe.2023.1099574

ISSN=2296-4185

ABSTRACT=<p><bold>Objective:</bold> Otitis media (OM) is an infectious and inflammatory disease of the middle ear (ME) that often recurs and requires long-term antibiotic treatment. Light emitting diode (LED)-based devices have shown therapeutic efficacy in reducing inflammation. This study aimed to investigate the anti-inflammatory effects of red and near-infrared (NIR) LED irradiation on lipopolysaccharide (LPS)-induced OM in rats, human middle ear epithelial cells (HMEECs), and murine macrophage cells (RAW 264.7).</p><p><bold>Methods:</bold> An animal model was established by LPS injection (2.0 mg/mL) into the ME of rats <italic>via</italic> the tympanic membrane. A red/NIR LED system was used to irradiate the rats (655/842 nm, intensity: 102 mW/m<sup>2</sup>, time: 30 min/day for 3 days and cells (653/842 nm, intensity: 49.4 mW/m<sup>2</sup>, time: 3 h) after LPS exposure. Hematoxylin and eosin staining was performed to examine pathomorphological changes in the tympanic cavity of the ME of the rats. Enzyme-linked immunosorbent assay, immunoblotting, and RT-qPCR analyses were used to determine the mRNA and protein expression levels of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Mitogen-activated protein kinases (MAPKs) signaling was examined to elucidate the molecular mechanism underlying the reduction of LPS-induced pro-inflammatory cytokines following LED irradiation.</p><p><bold>Results:</bold> The ME mucosal thickness and inflammatory cell deposits were increased by LPS injection, which were reduced by LED irradiation. The protein expression levels of IL-1β, IL-6, and TNF-α were significantly reduced in the LED-irradiated OM group. LED irradiation strongly inhibited the production of LPS-stimulated IL-1β, IL-6, and TNF-α in HMEECs and RAW 264.7 cells without cytotoxicity <italic>in vitro</italic>. Furthermore, the phosphorylation of ERK, p38, and JNK was inhibited by LED irradiation.</p><p><bold>Conclusion:</bold> This study demonstrated that red/NIR LED irradiation effectively suppressed inflammation caused by OM. Moreover, red/NIR LED irradiation reduced pro-inflammatory cytokine production in HMEECs and RAW 264.7 cells through the blockade of MAPK signaling.</p>