2. Academic Validation
  3. PVC Nanoplastics Exposure Exacerbates Asthma through R-Loop Accumulation and Subsequent STING Activation in Macrophages

PVC Nanoplastics Exposure Exacerbates Asthma through R-Loop Accumulation and Subsequent STING Activation in Macrophages

  • Adv Sci (Weinh). 2025 Sep 8:e02223. doi: 10.1002/advs.202502223.
Qimei Bao 1,  Yixing Huang 2 3,  Mingcong Deng 1,  Chunkai Zhang 1,  Dan Zu 4,  Hanyi He 5,  Yangchan Hu 5,  Yuke Zhong 1,  Chen Liang 1,  Haidong Liu 5 6 7,  Wumin Dai 1,  Yanhua He 5 6 7,  Yaoshu Teng 3,  Ji Jing 5 6 7,  Yin Shi 8,  Xiangdong Cheng 1 5 6 7,  Zu Ye 1 6 7 9 10
Affiliations

Affiliations

  • 1 Postgraduate training base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310022, China.
  • 2 Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 3 Department of Otorhinolaryngology, Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China.
  • 4 School of Life Sciences, Tianjin University, Tianjin, 300100, China.
  • 5 Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
  • 6 Key Laboratory of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer of Zhejiang Province, Hangzhou, 310022, China.
  • 7 Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, 310022, China.
  • 8 Department of Biochemistry, and Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
  • 9 Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, 530021, China.
  • 10 Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, 530021, China.
PMID: 40919700 DOI: 10.1002/advs.202502223
Abstract

Asthma is a chronic inflammatory respiratory disease influenced by genetic and environmental factors. Emerging evidence suggests that microplastics and nanoplastics (NPs) pose significant health risks. When inhaled, these tiny particles can accumulate in the lungs, triggering inflammation, oxidative stress, and Other disruptions in pulmonary function. This study investigates the role of polyvinyl chloride (PVC) NPs, which are extensively used in products such as packaging, medical devices, and construction Materials, in asthma pathogenesis. Using an ovalbumin (OVA)-induced murine asthma model, it is demonstrated that PVC NPs exposure exacerbates airway hyperresponsiveness, increases inflammatory cell infiltration, and elevates inflammatory cytokine levels in the lungs. Further mechanistic studies reveal that PVC NPs suppress Ribonuclease H1 (RNASEH1), leading to RNA-DNA hybrid loop (R-loop) accumulation and activation of the Cyclic GMP-AMP Synthase (cGAS)-Stimulator of Interferon Genes (STING) inflammatory pathway. The critical involvement of this pathway is confirmed using STING-deficient mice, where pathway inhibition alleviates the inflammation exacerbated by PVC NPs exposure. These findings provide new insights into the potential role of NPs pollutants in modulating immune responses through R-loop formation, linking PVC NPs to asthma pathogenesis. This study highlights the importance of addressing environmental exposure to NPs in asthma prevention and management and identifies potential molecular targets for therapeutic intervention.

Keywords

PVC nanoplastics; RNASEH1; R‐loops; STING activation; asthma.

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