Title : Impact of egg-derived proteins, yolkin polypeptide complex and ovocystatin, on blood-brain barrier integrity and function
Abstract:
Introduction: The blood-brain barrier (BBB) is a highly selective and protective membrane that separates the brain from the circulating blood, effectively shielding it from harmful substances, toxins and pathogens. Its primary function is to maintain brain homeostasis, regulate the movement of molecules and prevent the onset of neuroinflammation. The endothelial cells of the BBB play a critical role in this process. They have the ability to secrete cytokines in response to stress or inflammation, which helps to regulate the immune response and maintain the integrity of the barrier. When the integrity of the BBB is compromised or dysregulated, it can lead to a range of neurological disorders, highlighting the importance of maintaining its stability for brain health.
Aim: Egg-derived proteins, such as yolkin polypetide complex and ovocystatin, may serve as potential nutraceuticals that support BBB integrity and function.
Material and Methods: The effects of yolkin polypeptide complex and ovocystatin on BBB function/integrity were investigated. Human cerebral microvascular endothelial cells HBEC5i (ATCC) were used as an experimental model of the BBB. Cell viability was assessed using the MTT assay. Changes in tight junction (TJ) protein expression were determined by Western blotting. HBEC5i permeability (PE) measurements to the FITC-dextran molecule were assessed. Cytokine levels: TNFα, IL-1β, IL-6, IL-8 and IL-10 were determined by ELISA.
Results: Our study showed that yolkin and ovocystatin did not affect the viability of HBEC-5i cells. However, yolkin was found to modulate BBB permeability under inflammatory conditions as evidenced by changes in FITC-dextran permeability measurements. Western blot analysis showed no significant changes in TJ proteins, including ZO-1, E-cadherin and occludins. On the other hand, ELISA results showed that yolkin and ovocystatin selectively stimulated the secretion of IL-1β and IL-8 to the luminal side of the BBB, whereas no significant changes in the secretion of TNF-α, IL-6 or IL-10 were observed.
Conclusion: These findings suggest that yolkin and ovocystatin are non-toxic to the brain endothelial cells and affect BBB function by modulating permeability and cytokine production. By selectively stimulating the release of cytokines, such as proinflammatory IL-1β and chemotactic/angiogenic IL-8, they play a critical role in protecting and restoring BBB integrity during immune challenge.
