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MCC950 Ameliorates Acute Exogenous Lipoid Pneumonia Induced by Sewing Machine Oil in Rats via the NF-κB/NLRP3
Wan-Ding Ye1, Hua-Min Wang1, Zi-Jin Xu2
1Department of Pediatrics, Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, P.R. China.
Background/Aim:
Acute exogenous lipoid pneumonia (AELP) is a rare disorder caused by intake of lipid formulations and is often underdiagnosed. Meanwhile, the mechanism of AELP is still underlying. MCC950, was previously found to significantly suppress the release of inflammatory cytokines IL-18 and IL-1β. However, the effect of MCC950 on AELP induced by sewing machine oil has not been reported.
Materials And Methods:
The NLRP3, NF-[Formula: see text]B p65, caspase-1 and IL-1β expression in lung tissues were compared between a rat model of AELP and control rats using western blotting and real-time quantitative assay. Moreover, haematoxylin and eosin (H&E) staining was performed to elucidate the mechanisms by which MCC950 ameliorates sewing machine oil-induced AELP in vivo.
Results:
MCC950 reduced the expression of NF-[Formula: see text]B p65 in the lung samples of the treatment group and further down-regulated the NLRP3 and caspase-1 levels while inhibited the production of IL-1β. Besides, decreases in inflammatory cell infiltration in the lung were shown using H&E staining.
Conclusion:
MCC950 ameliorates sewing machine oil-induced acute exogenous lipoid pneumonia in rats through inhibition of the NF-[Formula: see text]B/NLRP3 inflammasome pathway.
Insights
MCC950 treatment reduced inflammation in rats with acute exogenous lipoid pneumonia (AELP) induced by sewing machine oil. This study shows MCC950 inhibits the NF-κB/NLRP3 inflammasome pathway, offering a potential therapeutic strategy for AELP.
Area of Science:
- Pulmonary Medicine
- Toxicology
- Pharmacology
Background:
- Acute exogenous lipoid pneumonia (AELP) is a rare, underdiagnosed condition resulting from lipid formulation intake.
- The precise mechanisms underlying AELP pathogenesis remain unclear.
- MCC950 is known to inhibit inflammatory cytokines IL-18 and IL-1β, but its effect on sewing machine oil-induced AELP was uninvestigated.
Purpose of the Study:
- To investigate the therapeutic effect of MCC950 on sewing machine oil-induced AELP in a rat model.
- To elucidate the underlying molecular mechanisms, particularly the involvement of the NF-κB/NLRP3 inflammasome pathway.
Main Methods:
- A rat model of AELP was established using sewing machine oil.
- Western blotting and real-time quantitative assays were used to measure NLRP3, NF-κB p65, caspase-1, and IL-1β expression.
- Hematoxylin and eosin (H&E) staining was performed to assess inflammatory cell infiltration.
Main Results:
- MCC950 treatment significantly reduced NF-κB p65 expression in lung tissues.
- MCC950 down-regulated NLRP3 and caspase-1 levels and inhibited IL-1β production.
- H&E staining revealed decreased inflammatory cell infiltration in the lungs of MCC950-treated rats.
Conclusions:
- MCC950 effectively ameliorates sewing machine oil-induced AELP in rats.
- The therapeutic effect is mediated by the inhibition of the NF-κB/NLRP3 inflammasome pathway.
- This study highlights MCC950 as a potential therapeutic agent for AELP.
