Mycobacteria induces pleural mesothelial permeability by down-regulating beta-catenin expression.
Patients with pulmonary tuberculosis develop pleural effusions with a high protein content. Pleural mesothelial adherens junctions promote mesothelial cell-cell adhesion and contribute to pleural integrity. In the present study we have investigated the effect of mycobacterium (BCG) on mesothelial cell adherens junction proteins and pleural permeability. BCG enhanced pleural mesothelial cell (PMC) release of vascular endothelial growth factor (VEGF), and decreased electrical resistance across the PMC monolayer. Neutralizing antibodies to VEGF significantly restored the drop in PMC electrical resistance caused by BCG. BCG infection down regulated beta-catenin (adherens junction protein) expression and caused increased permeability across confluent mesothelial monolayer. Our results suggest that in TB pleurisy, mycobacteria cause VEGF release from mesothelial cells and leads to protein exudation by altering mesothelial adherens junction proteins.
Mohammed
K A
KA
Department of Medicine, Veterans' Affairs Medical Center, Indiana University School of Medicine, 1481 West 10th Street, 111-P, Indianapolis, IN 46202, USA.
Nasreen
N
N
Hardwick
J
J
Van Horn
R D
RD
Sanders
K L
KL
Antony
V B
VB
D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D015536:Down-Regulation; D017097:Electric Impedance; D016228:Endothelial Growth Factors / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D009163:Mycobacterium bovis; D010539:Permeability; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis*; D014396:Tuberculosis, Pleural / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D012333:RNA, Messenger; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051176:beta Catenin