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

Yoo-Seung Ko; Eun-Ji Gi; Sungsu Lee; Hyong-Ho Cho

doi:10.3389/fbioe.2023.1099574

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

Front Bioeng Biotechnol. 2023 Feb 22:11:1099574. doi: 10.3389/fbioe.2023.1099574. eCollection 2023.

Authors

Yoo-Seung Ko¹, Eun-Ji Gi^{1

2}, Sungsu Lee¹, Hyong-Ho Cho¹

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School and Chonnam National University Hospital, Gwangju, Republic of Korea.
² Department of Biomedical Science, College of Medicine, Chonnam National University Graduate School, BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, Republic of Korea.

Abstract

Objective: 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). Methods: An animal model was established by LPS injection (2.0 mg/mL) into the ME of rats via the tympanic membrane. A red/NIR LED system was used to irradiate the rats (655/842 nm, intensity: 102 mW/m², time: 30 min/day for 3 days and cells (653/842 nm, intensity: 49.4 mW/m², 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. Results: 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 in vitro. Furthermore, the phosphorylation of ERK, p38, and JNK was inhibited by LED irradiation. Conclusion: 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.

Keywords: infection; inflammation; light emitting diode; near infrared; otitis media.

Grants and funding

This study was supported by a grant (HR20C0021) from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea, a hospital-based business innovation center grant, and a Chonnam National University Hospital Biomedical Research Institute grant (No. BCRI22084). The LED irradiation system was kindly designed and provided by Kang Wook Yoon and Jung Hyun Lee at HK HEALTHcare Co., Ltd., Korea.