Honokiol ameliorates silica-induced lung fibrosis by inhibiting macrophage pyroptosis via modulating cGAS/STING signaling

Qiang Zhou; Meiyu Chang; Shuhan Guo; Yiming Zhang; Qiufang Qu; Qingnan Zhou; Zhiheng Li; Sanqiao Yao

doi:10.1016/j.intimp.2024.113812

Honokiol ameliorates silica-induced lung fibrosis by inhibiting macrophage pyroptosis via modulating cGAS/STING signaling

Int Immunopharmacol. 2024 Dec 15:146:113812. doi: 10.1016/j.intimp.2024.113812. Online ahead of print.

Authors

Qiang Zhou¹, Meiyu Chang², Shuhan Guo³, Yiming Zhang³, Qiufang Qu³, Qingnan Zhou³, Zhiheng Li⁴, Sanqiao Yao⁵

Affiliations

¹ School of Public Health, Xinxiang Medical University, Xinxiang 453003, China; School of Public Health, North China University of Science and Technology, Tangshan 063000, China.
² School of Public Health, North China University of Science and Technology, Tangshan 063000, China.
³ School of Public Health, Xinxiang Medical University, Xinxiang 453003, China.
⁴ Institution for Occupational Disease Prevention and Treatment of China Pingmei Shenma Group, Pingdingshan 462500, China.
⁵ School of Public Health, Xinxiang Medical University, Xinxiang 453003, China; School of Public Health, North China University of Science and Technology, Tangshan 063000, China. Electronic address: sanqiaoyao@126.com.

PMID: 39681061
DOI: 10.1016/j.intimp.2024.113812

Abstract

Silicosis is a life-threatening occupational disease because of inhaling silica dust, leading to chronic inflammation, pyroptosis, and fibrosis. Unfortunately, it is still lacking effective pharmacological intervention currently. Honokiol (HKL), a natural extract with biological activity from Magnolia bark, is known for its antioxidant and anti-inflammatory biological effects. The current work aimed to investigate the therapeutic potential of HKL in mitigating silica-induced lung fibrosis and pyroptosis, particularly focusing on the cGAS/STING signaling pathway. The pulmonary pathological results shown in H&E and Masson's trichrome staining images confirmed the protective effects of HKL on lung tissue structure. In addition, HKL significantly reduced lung inflammation, collagen deposition, and oxidative stress compared to mice in the silicosis group. HKL treatment also alleviated silica-induced pyroptosis by suppressing the activation of the cGAS/STING signaling pathway in lung tissues. Moreover, the in vitro experiments using J774A.1 macrophages demonstrated that HKL reduced pyroptosis and improved cell viability under exposure to silica combined lipopolysaccharide (LPS). These were attributed to HKL downregulating the activation of the cGAS/STING signaling pathway in pyroptotic J774A.1 cells induced by silica combined with LPS. Meanwhile, inhibition of STING signaling induced by DNase I significantly enhanced the protective effects of HKL on the inflammatory and pyroptotic processes induced by silica. Overall, HKL could attenuate silica-induced pyroptosis by modulating the cGAS/STING signaling pathway against pulmonary fibrosis. The current study offers a promising approach for treating silicosis and related inflammatory responses.

Keywords: Honokiol; Inflammation; Pyroptosis; Silicosis; cGAS/STING pathway.