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Ficolin-2 amplifies inflammation in macrophage-smooth muscle cell cross-talk and increases monocyte transmigration by mechanisms involving IL-1β and IL-6

Ficolin-2, recently identified in atherosclerotic plaques, has been correlated with future acute cardiovascular events, but its role remains unknown. We hypothesize that it could influence plaque vulnerability by interfering in the cross-talk between macrophages (MØ) and smooth muscle cells (SMC). T...

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Bibliographic Details
Published in:Scientific reports 2023-11, Vol.13 (1), p.19431-19431, Article 19431
Main Authors: Macarie, Răzvan Daniel, Tucureanu, Monica Mădălina, Ciortan, Letiția, Gan, Ana-Maria, Butoi, Elena, Mânduțeanu, Ileana
Format: Article
Language:English
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Summary:Ficolin-2, recently identified in atherosclerotic plaques, has been correlated with future acute cardiovascular events, but its role remains unknown. We hypothesize that it could influence plaque vulnerability by interfering in the cross-talk between macrophages (MØ) and smooth muscle cells (SMC). To examine its role and mechanism of action, we exposed an in-vitro co-culture system of SMC and MØ to ficolin-2 (10 µg/mL) and then performed cytokine array, protease array, ELISA, qPCR, Western Blot, and monocyte transmigration assay. Carotid plaque samples from atherosclerotic patients with high plasma levels of ficolin-2 were analyzed by immunofluorescence. We show that ficolin-2: (i) promotes a pro-inflammatory phenotype in SMC following interaction with MØ by elevating the gene expression of MCP-1, upregulating gene and protein expression of IL-6 and TLR4, and by activating ERK/MAPK and NF-KB signaling pathways; (ii) increased IL-1β, IL-6, and MIP-1β in MØ beyond the level induced by cellular interaction with SMC; (iii) elevated the secretion of IL-1β, IL-6, and CCL4 in the conditioned medium; (iv) enhanced monocyte transmigration and (v) in atherosclerotic plaques from patients with high plasma levels of ficolin-2, we observed co-localization of ficolin-2 with SMC marker αSMA and the cytokines IL-1β and IL-6. These findings shed light on previously unknown mechanisms underlying ficolin-2–dependent pathological inflammation in atherosclerotic plaques.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-46770-0