Effects of tumor necrosis factor alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells.

Duchini, A.; Govindarajan, S.; Santucci, Marco; Zampi, Giancarlo; Hofman, F. M.

Abstract BACKGROUND: Proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play an important role in the blood-brain barrier breakdown present in several neurological diseases including multiple sclerosis and AIDS. However, the specific effects of these cytokines on central nervous system-derived endothelial cells (CNS-EC) is not fully understood. In this study the effects of TNF-alpha and IL-6 were tested on different permeability mechanisms of CNS-EC. METHODS: Central nervous system endothelial cells were isolated from human brain and retina and cultured in vitro in a transwell system. Fluid-phase endocytosis and transcytosis, absorptive-mediated endocytosis, and ammonia diffusion were measured with specific methods. Endothelial cells were studied with electron microscopy for the ultrastructural effects of cytokine stimulation. RESULTS: Fluid-phase endocytosis and transcytosis were significantly increased by TNF-alpha and IL-6. This effect was dose dependent and reversible. The ammonia diffusion rate was also significantly increased by TNF-alpha. Absorptive-mediated endocytosis was not enhanced by TNF-alpha. Ultrastructural analysis of cytokine-treated CNS-EC confirmed the alterations in permeability showing an increase in endocytotic activity and a decrease in tight junctions. CONCLUSIONS: The proinflammatory cytokines IL-6 and TNF-alpha induce specific changes in the morphology and permeability of CNS-EC. These alterations can be important in many diseases characterized by increased cytokine production.

Effects of tumor necrosis factor alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells / DUCHINI A.; GOVINDARAJAN S.; SANTUCCI M.; G. ZAMPI; HOFMAN F.M.. - In: JOURNAL OF INVESTIGATIVE MEDICINE. - ISSN 1081-5589. - STAMPA. - 44(1996), pp. 474-482.

trova@unifi

Titolo:	Effects of tumor necrosis factor alpha and interleukin-6 on fluid-phase permeability and ammonia diffusion in CNS-derived endothelial cells.
Autori di Ateneo:	DUCHINI A. GOVINDARAJAN S. SANTUCCI, MARCO ZAMPI, GIANCARLO HOFMAN F. M. mostra contributor esterni nascondi contributor esterni
Autori:	DUCHINI A.; GOVINDARAJAN S.; SANTUCCI, MARCO; ZAMPI, GIANCARLO; HOFMAN F. M.
Anno di registrazione:	1996
Rivista:	JOURNAL OF INVESTIGATIVE MEDICINE
Volume:	44
Pagina iniziale:	474
Pagina finale:	482
Abstract:	Abstract BACKGROUND: Proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) play an important role in the blood-brain barrier breakdown present in several neurological diseases including multiple sclerosis and AIDS. However, the specific effects of these cytokines on central nervous system-derived endothelial cells (CNS-EC) is not fully understood. In this study the effects of TNF-alpha and IL-6 were tested on different permeability mechanisms of CNS-EC. METHODS: Central nervous system endothelial cells were isolated from human brain and retina and cultured in vitro in a transwell system. Fluid-phase endocytosis and transcytosis, absorptive-mediated endocytosis, and ammonia diffusion were measured with specific methods. Endothelial cells were studied with electron microscopy for the ultrastructural effects of cytokine stimulation. RESULTS: Fluid-phase endocytosis and transcytosis were significantly increased by TNF-alpha and IL-6. This effect was dose dependent and reversible. The ammonia diffusion rate was also significantly increased by TNF-alpha. Absorptive-mediated endocytosis was not enhanced by TNF-alpha. Ultrastructural analysis of cytokine-treated CNS-EC confirmed the alterations in permeability showing an increase in endocytotic activity and a decrease in tight junctions. CONCLUSIONS: The proinflammatory cytokines IL-6 and TNF-alpha induce specific changes in the morphology and permeability of CNS-EC. These alterations can be important in many diseases characterized by increased cytokine production.
Handle:	http://hdl.handle.net/2158/310478
Appare nelle tipologie:	1a - Articolo su rivista

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