Mycobacteria induces pleural mesothelial permeability by down-regulating beta-catenin expression

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Immunology

Background:

• Tuberculosis (TB) pleurisy is characterized by high-protein pleural effusions.
• Pleural mesothelial cells form adherens junctions, crucial for pleural barrier integrity.
• The impact of mycobacteria on these junctions and pleural permeability is not fully understood.

Purpose of the Study:

• To investigate the effect of mycobacterium (BCG) on mesothelial cell adherens junction proteins.
• To determine the impact of BCG on pleural permeability.
• To elucidate the role of vascular endothelial growth factor (VEGF) in BCG-induced pleural changes.

Main Methods:

• Treatment of pleural mesothelial cells (PMCs) with BCG.
• Measurement of VEGF release from PMCs.
• Assessment of electrical resistance across PMC monolayers as a measure of permeability.
• Analysis of beta-catenin expression.
• Use of neutralizing antibodies to VEGF.

Main Results:

• BCG enhanced PMC release of VEGF.
• BCG decreased electrical resistance across PMC monolayers, indicating increased permeability.
• Neutralizing VEGF antibodies partially restored PMC electrical resistance.
• BCG infection downregulated beta-catenin expression.
• BCG caused increased permeability across confluent mesothelial monolayers.

Conclusions:

• Mycobacteria induce VEGF release from mesothelial cells in TB pleurisy.
• VEGF and altered adherens junction proteins (like beta-catenin) contribute to increased pleural permeability.
• These changes facilitate protein exudation into the pleural space in TB pleurisy.