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Published on: July 6, 2019
Microcystin-LR induces lung injury in mice through the NF-κB/NLRP3 pathway
Yin Zhang1, Ying Guan1, Manni Dai1
1Hunan Province Key Laboratory of Typical Environmental Pollution and Health Hazards, School of Public Health, Hengyang Medical School, University of South China, Hengyang, Hunan, China.
Abstract:
Microcystin-LR (MC-LR) a cyclic toxin produced by cyanobacterial species is known to exert detrimental effects on various organs, including lung. Several investigators demonstrated that MC-LR exerts pulmonary toxicity, but the underlying mechanisms remain unclear. This study aimed to investigate whether exposure to MC-LR-induced lung inflammation and examine the underlying mechanisms. Thirty specific pathogen-free (SPF) male mice were allocated into control and MC-LR treatment groups. Mice were intraperitoneally injected with physiological saline or MC-LR (20 μg/kg) daily for a total of 21 days. Our findings indicated that exposure to MC-LR-produced histopathological changes in lung tissue, including thickening of alveolar walls and inflammatory infiltration. MC-LR was found to upregulate mRNA expression levels of pro-inflammatory cytokines TNFα, IL-6, IL-1β, and IL-18. Further, MC-LR significantly elevated the expression levels of proteins associated with the NF-κB/NLRP3 pathway p-NF-κB, NLRP3, Caspase-1, ASC. The activation of NF-κB/NLRP3 pathway further promoted the release of inflammatory cytokine IL-1β and cleavage of pyroptosis-associated GSDMD protein. These findings indicate that MC-LR may induce lung inflammation by promoting cell pyroptosis via the activation of the NF-κB/NLRP3 pathway.
Insights
Microcystin-LR (MC-LR) causes lung inflammation by activating the NF-κB/NLRP3 pathway, leading to pyroptosis. This study clarifies the mechanisms behind MC-LR-induced pulmonary toxicity.
Area of Science:
- Environmental Toxicology
- Pulmonary Medicine
- Cellular Biology
Background:
- Cyanobacterial blooms produce Microcystin-LR (MC-LR), a toxin impacting various organs, including the lungs.
- While MC-LR's pulmonary toxicity is known, the precise mechanisms remain incompletely understood.
Purpose of the Study:
- To investigate MC-LR-induced lung inflammation.
- To elucidate the underlying molecular mechanisms, focusing on inflammatory pathways and cell death.
Main Methods:
- Specific pathogen-free male mice were administered MC-LR (20 μg/kg) or saline daily for 21 days.
- Lung tissues were analyzed for histopathological changes, pro-inflammatory cytokine mRNA expression (TNFα, IL-6, IL-1β, IL-18), and key proteins in the NF-κB/NLRP3 pathway (p-NF-κB, NLRP3, Caspase-1, ASC).
Main Results:
- MC-LR exposure induced lung histopathology, including thickened alveolar walls and inflammatory cell infiltration.
- MC-LR upregulated pro-inflammatory cytokines and activated the NF-κB/NLRP3 pathway, evidenced by increased p-NF-κB, NLRP3, Caspase-1, and ASC.
- Pathway activation promoted IL-1β release and pyroptosis marker GSDMD cleavage.
Conclusions:
- MC-LR induces lung inflammation and histopathological damage.
- The NF-κB/NLRP3 pathway activation is a key mechanism in MC-LR-induced lung inflammation.
- MC-LR promotes lung cell pyroptosis via the NF-κB/NLRP3 pathway.
