Abstract
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) with pathophysiologic features similar to multiple sclerosis (MS). In both diseases circulating leukocytes penetrate the blood-brain barrier and damage myelin, resulting in impaired nerve conduction and paralysis. The pluripotent cytokine tumor necrosis factors (TN-F-a), has been implicated to play an important role in the pathogenesis of MS and EAE. TNIF-(X may act by promoting leukocyte adhesion to the cerebrovascular endothelium (CVE) and migration of inflammatory cells into the CNS. The receptors for TNF (TNFR) on CVE cells may be a potential target for therapeutic intervention. In order to examine the role of the TNF receptors, CVE cell lines were established from EAE susceptible (SJL/J) and resistant (BALB/c) inbred strains of mice. The lines retained endothelial cell specific markers and remained diploid through 16 passages. An endothelial cell specific CDNA library was synthesized and the 55 kD and 75 kD TNF receptors were cloned and sequenced. Quantitative northern blotting was used to determine the effects of IIFN-Y, IL-1, and TNF-(X on CVE cell TNFR MRNA regulation using TNFR specific hybridization probes. IFN-Y and IL- 1 were found to increase niRNA transcription of the 55 kD and 75 kD TNFR. The 55 kD receptor was more sensitive to up-regulation by IFN-,y, whereas the 75 kD receptor was more sensitive to up-regulation by EL- 1. IL- 1 and TNF-(X were found to act in a cooperative manner to up-regulate MRNA for both the 55kD and 75 kD receptors. No significant differences were found in cytokine induced TNFR MRNA levels between SJL/J and BALB/c CVE that might explain differences in EAE susceptibility. However, in studies of mast cells derived from these mouse strains, it was found that SJL/J mast cells store and release significantly more TNF-A and histamine than BALB/c mast cells. These studies suggest that the levels of cytokines, such as TN-F-a, released by CNS associated mast cells, may contribute to susceptibility differences in murine EAE.
Bebo, Bruce Frank (1995). Cytokine regulation of tumor necrosis factor receptor messenger RNA in mouse cerebromicrovascular endothelial cells. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -1559622.