Endothelial-monocyte-activating polypeptide II increases blood-tumor barrier permeability by down-regulating the expression levels of tight junction associated proteins

This study was performed to determine whether endothelial-monocyte-activating polypeptide (EMAP) II increases the permeability of the blood-tumor barrier (BTB) in the rat model of C6 glioma, and whether EMAP II opens the BTB by affecting tight junction (TJ) associated proteins zonula occluden-1 (ZO-1), occludin and claudin-5. The rats were divided into eight groups randomly: control group, EMAPII 0 h group, EMAPII 0.5 h group, EMAPII 1 h group, EMAPII 2 h group, EMAPII 3 h group, EMAPII 6 h group and EMAPII 12 h group. The BTB permeability was assessed by Evans blue extravasation. The mRNA and protein expressions of ZO-1, occludin, and claudin-5 were determined by reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemistry assays. The BTB permeability significantly increased after EMAP II injection in different doses (40 ng/kg, 80 ng/kg and 160 ng/kg). The BTB permeability started to increase from 0.5 h, reached a peak at 1 h, and finally returned to the level of EMAP II 0 h group after EMAP II injection at dose of 80 ng/kg. The mRNA and protein expression levels of ZO-1, occludin and claudin-5 were significantly decreased after EMAP II injection. This study demonstrates for the first time that EMAP II increases the permeability of BTB selectively, and the possible mechanism is associated with the down-regulation of ZO-1, occludin and claudin-5. (C) 2010 Elsevier B.V. All rights reserved.