BK Channels Regulate LPS-induced CCL-2 Release from Human Pulmonary Endothelial Cells

Area of Science:

• Cardiovascular Science
• Pulmonary Science
• Cell Biology

Background:

• TREK-1 channels regulate inflammatory cytokine secretion in acute lung injury.
• Large conductance, calcium-activated potassium (BK) channels are expressed in pulmonary endothelial and alveolar epithelial cells.

Purpose of the Study:

• Investigate the role of BK channels in lipopolysaccharide (LPS)-induced acute lung injury.
• Determine if BK channel activation can modulate inflammatory cytokine secretion.

Main Methods:

• Semiquantitative real-time PCR, IP, and Western blot to detect BK channel expression.
• LPS-induced acute lung injury model in human pulmonary microvascular endothelial cells and primary human alveolar epithelial cells.
• BK channel activation (NS1619) and inhibition (Paxilline) to assess effects on cytokine secretion and membrane potential.

Main Results:

• LPS induced IL-6 and CCL-2 secretion from pulmonary cells.
• BK channel activation decreased LPS-induced CCL-2 secretion in endothelial cells but not IL-6 or epithelial cell secretion.
• BK channel activation hyperpolarized the plasma membrane potential in both cell types, independent of intracellular calcium.
• BK channel inhibition did not affect cytokine secretion or membrane potential.

Conclusions:

• BK channel activation is a potential therapeutic strategy to reduce CCL-2 secretion in LPS-induced lung injury.
• The protective effect of BK channel activation is mediated by plasma membrane hyperpolarization, independent of intracellular calcium levels.