Figure 3.

TLR2-mediated Ca²⁺ fluxes activate calpains, which cleave junctional proteins and facilitate PMN transmigration. Bacterial detection by TLR2 mediates a Ca²⁺ release that signals IL-8 expression to recruit PMNs and also initiates modifications to the epithelial junctions to facilitate PMN transmigration. TLR2-mediated Ca²⁺ fluxes activate calpains that target the transmembrane junctional proteins, occludin and E-cadherin. Calpain activation is inhibited in TLR2 siRNA-expressing cells. Occludin and E-cadherin cleavage is blocked in airway cells expressing a TLR2 tyrosine mutant or calpain siRNA oligonucleotides. Occludin and E-cadherin cleavage and PMN migration across airway cells are blocked by calpain inhibitors.