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Zhang Y, Huang S, Tan S, et al. 3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway. Toxicol Ind Health. 2021;37(11):662-673doi: 10.1177/07482337211039426.
Zhang, Y., Huang, S., Tan, S., Chen, M., Yang, S., & Chen, S. (2021). 3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway. Toxicology and industrial health, 37(11), 662-673. https://doi.org/10.1177/07482337211039426
Zhang, Yujing, et al. "3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway." Toxicology and industrial health vol. 37,11 (2021): 662-673. doi: https://doi.org/10.1177/07482337211039426
Zhang Y, Huang S, Tan S, Chen M, Yang S, Chen S. 3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway. Toxicol Ind Health. 2021 Nov;37(11):662-673. doi: 10.1177/07482337211039426. Epub 2021 Sep 25. PMID: 34565256.
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Toxicol Ind Health. 2021 Nov;37(11):662-673. doi: 10.1177/07482337211039426. Epub 2021 Sep 25.

3-methyadenine inhibits lipopolysaccharides-induced pulmonary inflammation at the early stage of silicosis via blocking NF-κB signaling pathway.

Toxicology and industrial health

Yujing Zhang, Shuai Huang, Shiyi Tan, Mingke Chen, Shang Yang, Shi Chen

Affiliations

  1. Key Laboratory of Molecular Epidemiology of Hunan Province, 12568Hunan Normal University, Changsha, Hunan Province, China.

PMID: 34565256 DOI: 10.1177/07482337211039426

Abstract

Occupational exposure to silica dust is related to pulmonary inflammation and silicosis. Lipopolysaccharides (LPSs) could aggravate apoptosis in alveolar macrophages (AMs) of human silicosis through autophagy, yet how the reduction of autophagy attenuated LPS-induced lung injury and the related mechanisms need to be investigated. In the study, we aim to understand the role of 3-methyladenine (3-MA), an inhibitor of autophagy, in LPS-mediated inflammatory responses and fibrosis. We collected AMs from observers/silicosis patients. The results showed that LPS induced NF-κB-related pulmonary inflammation in observers and silicosis patients, as confirmed by an increase in the expression of IL-1β, IL-6, TNF-α, and p65, which could be inhibited by 3-MA treatment. In mice models, at the early stage (7d) of silicosis, but not the late (28d) stage, blocking autophagy reversed the increased levels of IL-1β, IL-6, TNF-α, and p65 caused by LPS. Mechanism study revealed that LPS triggered the expression of LC3 II, p62, and cleaved caspase-3 at the early stage exposed to silica, which could be restored by 3-MA, while there was no difference in the expression of LAMP1 either at the early or late stage of silicosis in different groups. Similarly, 3-MA treatment did not prevent fibrosis characterized by destroyed alveoli, collagen deposition, and increased expression of α-SMA and Col-1 induced by LPS at the late stage of silicosis. The results suggested that 3-MA has a role in the protection of lung injury at the early stage of silicosis and provided an experimental basis for preventive strategies of pulmonary inflammation and silicosis.

Keywords: 3-MA; NF-κB; Silicosis; alveolar macrophages; inflammatory responses

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