Cooperation between Classical and Alternative NF-κB Pathways Regulates Proinflammatory Responses in Epithelial Cells

摘要: The transcription factor NF-κB has been causally linked to inflammatory lung diseases. Recent studies have unraveled the complexity of activation by identifying two parallel pathways: classical pathway, which is controlled IκB kinase complex–β (IKKβ) and RelA/p50, alternative IKKα RelB/p52. pathway regulates adaptive immune responses lymphoid development, yet its role in regulation innate remains largely unknown. In this study, we determined relevance proinflammatory epithelial cells. exposure C10 murine alveolar cells diverse stimuli, or primary tracheal LPS, resulted both pathways, based on nuclear translocation RelA, p50, RelB, p52. Increases content RelA occurred rapidly, but transiently, whereas increases RelB were protracted. small interfering (si) RNA–mediated knockdown IKKα, decreases multiple LPS-induced cytokines. Surprisingly, siRNA ablation led marked production IL-6 response LPS. simultaneous expression constitutively active (CA)-IKKα CA-IKKβ caused synergistic mediators. Lastly, disruption IKK signalsome inhibited pathways. These results demonstrate that coordinated pathways magnitude nature