Strain-specific variation in constitutive and inducible expression of MHC class II, class I and ICAM-1 on rat cerebral endothelium.

ABSTRACT

Strain variation in levels of inducible major histocompatibility complex (MHC) class II expression by rat cerebral endothelium has previously been reported. Using primary cell cultures of rat cerebral endothelium from PVG (RT1c), LEW (RT1l), PVG.LEW (RT1l) and PVG.AGUS (RT1lv?) strains it was determined that variation in levels of inducible MHC class II expression between strains can be accounted for by both cis-acting elements within the MHC region and by trans-acting elements outside the MHC. In addition it was determined that levels of constitutive MHC class I expression varied between PVG (RT1c) and LEW (RT1l) strains which can be attributed to cis-acting elements within the MHC region. Furthermore, while levels of constitutive class I expression vary between PVG (RT1c) and LEW (RT1l) endothelium we could find no difference in the interferon-gamma (IFN-gamma) inducible expression of class I between these two strains. In contrast the inducibility of intercellular adhesion molecule-1 (ICAM-1) in response to IFN-gamma was found to differ between PVG and LEW endothelium. Significant levels of ICAM-1 are induced on LEW cerebral endothelium after 24 hr exposure to 50 U/ml IFN-gamma. However, no significant induction of ICAM-1 could be demonstrated on PVG, or BN cerebral endothelium after the same exposure to IFN-gamma. Induction of ICAM-1 by IFN-gamma precedes MHC class II by at least 24 hr and its persistence is proportional to the concentration of IFN-gamma used. We suggest that the rat MHC region (RT1) contains elements which control the levels of constitutive class I expression and inducible class II expression in response to IFN-gamma, but that other non-RT1 genes influence the inducibility of MHC class II on rat cerebral endothelial cells. This observation, together with the finding that ICAM-1 expression is not significantly increased in response to IFN-gamma on PVG or BN endothelium, suggests that IFN-gamma responsiveness by these strains differs from LEW.