When human aortic endothelial cells are grown in stacked layers instead of a single layer, they produce significantly higher levels of IL-6, MCP-1, and CXCL8 messenger RNA and proteins after 11 days...
Mechanism
Synthesis from 1 study
When endothelial cells are stacked on top of each other, their internal machinery gets scrambled, causing key protein-making parts to move into the nucleus. This switch turns up the production of inflammatory signals, which flood out of the cells in large amounts.
Most probable mechanism
When endothelial cells are piled up in three dimensions, their internal structure gets disrupted, causing parts of their protein-making machinery to move into the nucleus. This shift activates a surge in the production of inflammatory signals, which are then released into the surrounding environment.
Physical stacking of endothelial cells disrupts cytoskeletal organization, leading to loss of normal cell shape and reduced actin filament density.
Disrupted cytoskeletal architecture causes Golgi apparatus components and COPII vesicles to translocate from the cytoplasm into the nucleus.
Nuclear translocation of Golgi components facilitates the movement of ribosomal protein RPL23 into the nucleolus, where it accumulates and alters ribosomal biogenesis.
RPL23 accumulation in the nucleolus enhances translational capacity, increasing the synthesis of mRNA transcripts for IL-6, MCP-1, and CXCL8.
Elevated levels of IL-6, MCP-1, and CXCL8 mRNA are translated into protein and secreted from the cell at significantly increased rates.
Evidence from Studies
Supporting (1)
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Stacked human aortic endothelial cells induce atherosclerotic fatty streaks and release proinflammatory cytokines and chemokines
Contradicting (0)
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