bix-01294 and Inflammation

A shock-and-kill approach involving the simultaneous treatment of HIV-1-infected patients with latency-reversing agents (LRAs) and combination antiretroviral therapy was proposed as a means to eradicate viral reservoirs. Currently available LRAs cannot discriminate between HIV-1-infected and uninfected cells. Therefore, the risks and benefits of using broad-spectrum LRAs need to be carefully evaluated, particularly in the CNS, where inflammation and leukocyte transmigration must be tightly regulated. We used a real-time impedance-sensing system to dynamically record the impact of different classes of LRAs on the integrity of tight monolayers of the immortalized human cerebral microvascular endothelial cell line hCMEC/D3. Results show that prostratin and bryostatin-1 can significantly damage the integrity of an endothelial monolayer. Moreover, prostratin and bryostatin-1 induce secretion of some proinflammatory cytokines and an increase of ICAM-1 expression. Additional studies demonstrated that prostratin and bryostatin-1 also affect adhesion and transmigration of CD4

Topics: Acetamides; Azacitidine; Azepines; Blood-Brain Barrier; Bryostatins; Cell Adhesion; Cell Adhesion Molecules; Cell Movement; Cells, Cultured; Chemokine CCL2; Cytokines; Decitabine; HIV-1; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leukocytes; Phorbol Esters; Quinazolines; Receptors, Cell Surface; Virus Latency