Faculty Collaboration Database

TGF-beta 2 decreases migration of lymphocytes in vitro and homing of cells into the central nervous system in vivo. J Immunol 1995 Jul 01;155(1):325-32

Date

07/01/1995

Pubmed ID

7602108

Scopus ID

2-s2.0-0028982243 (requires institutional sign-in at Scopus site)   92 Citations

Abstract

Migration of leukocytes through an in vitro, cell culture model of the blood-brain barrier (BBB) composed of murine brain microvessel endothelial (En) cells and astrocytes, and in vivo in experimental allergic encephalomyelitis (EAE), was investigated. We have recently shown that the adhesiveness of cultured murine brain microvascular endothelial cells for lymphocytes can be increased significantly by pretreatment with IL-1 beta, TNF-alpha, IFN-gamma, and LPS. In the present study, we investigated the role of TGF-beta 2 on the migration of leukocytes through the BBB. In vitro migration was assessed by measuring the percentage of 51Cr-labeled leukocytes migrating through the En/astrocyte monolayers. The basal level of migration was up-regulated significantly by treating the En/astrocyte monolayers with IL-1 alpha, IFN-gamma, TNF-alpha, and LPS. The ability of these cytokines to modulate migration was dose-dependent. Treatment of En cell/astrocyte monolayers with TGF-beta 2 down-regulated the level of leukocyte migration up-regulated by IL-1 alpha, IFN-gamma, and TNF-alpha in vitro in a dose-dependent manner. TGF-beta 2 also inhibited the migration of lymphocytes into the central nervous system (CNS) in vivo in a dose-dependent fashion. Taken together, these findings strongly suggest that TGF-beta plays an important role in the reduction of lymphocyte infiltration into the CNS in inflammatory demyelinating diseases such as EAE.

Author List

Fabry Z, Topham DJ, Fee D, Herlein J, Carlino JA, Hart MN, Sriram S

Author

Dominic B. Fee MD Vice Chair, Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood-Brain Barrier
Cell Adhesion
Cell Movement
Cells, Cultured
Central Nervous System
Dose-Response Relationship, Immunologic
Down-Regulation
Encephalomyelitis, Autoimmune, Experimental
Endothelium, Vascular
Female
Leukocytes
Lymphocytes
Mice
Mice, Inbred Strains
Receptors, Lymphocyte Homing
Transforming Growth Factor beta