성예원 (NIH)

한빛사논문

조회291

NIH

Sci. Adv., Jul 26 2024, 10 (30) eadk9878 | https://doi.org/10.1126/sciadv.adk9878 Macrophage depletion protects against cisplatin-induced ototoxicity and nephrotoxicity

Cathy Yea Won Sung ^1*, Naoki Hayase ², Peter S. T. Yuen ², John Lee ¹, Katharine Fernandez ¹, Xuzhen Hu ², Hui Cheng ³, Robert A. Star ², Mark E Warchol ⁴, Lisa L. Cunningham ^1*

¹Laboratory of Hearing Biology and Therapeutics, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.

²Renal Diagnostics and Therapeutics Unit, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH, Bethesda, MD, USA.

³Bioinformatics and Biostatistics Collaboration Core, National Institute on Deafness and Other Communication Disorders (NIDCD), NIH, Bethesda, MD, USA.

⁴Department of Otolaryngology, School of Medicine, Washington University, Saint Louis, MO, USA.

^*Corresponding authors: C.Y.W.S., L.L.C.

Abstract

Cisplatin is a widely used anticancer drug with notable side effects including ototoxicity and nephrotoxicity. Macrophages, the major resident immune cells in the cochlea and kidney, are important drivers of both inflammatory and tissue repair responses. To investigate the roles of macrophages in cisplatin-induced toxicities, we used PLX3397, a U.S. Food and Drug Administration-approved inhibitor of the colony-stimulating factor 1 receptor, to eliminate tissue-resident macrophages. Mice treated with cisplatin alone had considerable hearing loss (ototoxicity) and kidney injury (nephrotoxicity). Macrophage ablation resulted in significantly reduced hearing loss and had greater outer hair cell survival. Macrophage ablation also protected against cisplatin-induced nephrotoxicity, as evidenced by markedly reduced tubular injury and fibrosis. Mechanistically, our data suggest that the protective effect of macrophage ablation against cisplatin-induced ototoxicity and nephrotoxicity is mediated by reduced platinum accumulation in both the inner ear and the kidney. Together, our data indicate that ablation of tissue-resident macrophages represents an important strategy for mitigating cisplatin-induced ototoxicity and nephrotoxicity.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-08-07)
연구진국외 연구진
분야

댓글 작성 로그인

CV 열람하기

연락처 보기