Figure 12.

Proposed scheme of the intracellular pathways involved in lipopolysaccharide (LPS)-induced activation of canonical NF-κB pathway. LPS treatment results in activation of the toll-like receptor (TLR)-4 signal transduction and myeloid differentiation primary response (MyD)88-dependent signaling cascade. Activation of TLR-4/MyD88 signal transduction pathway leads to the activation of IL-1 receptor-associated kinase (IRAK)-4 and phosphorylation of transforming growth factor-β–activating kinase (TAK)-1, leading to the activation of canonical NF-κB pathway of both inhibitory κ B (IκB) kinases (IKKs), IKK-α and IKK-β, which further leads to degradation of IκB-α and nuclear translocation of NF-κB p65/p50. The activation of TAK-1 and canonical NF-κB p65/p50 causes up-regulation of myosin light chain kinase (MLCK) gene and protein expression, ultimately increasing tight junction (TJ) permeability in vitro and in vivo.