Transcriptional mechanisms of acute lung injury

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Abstract
Acute lung injury occurs as a result of a cascade of cellular events initiated by either infectious or noninfectious inflammatory stimuli. An elevated level of proinflammatory mediators combined with a decreased expression of anti-inflammatory molecules is a critical component of lung inflammation. Expression of proinflammatory genes is regulated by transcriptional mechanisms. Nuclear factor-κB (NF-κB) is one critical transcription factor required for maximal expression of many cytokines involved in the pathogenesis of acute lung injury. Activation and regulation of NF-κB are tightly controlled by a complicated signaling cascade. In acute lung injury caused by infection of bacteria, Toll-like receptors play a central role in initiating the innate immune system and activating NF-κB. Anti-inflammatory cytokines such as interleukin-10 and interleukin-13 have been shown to suppress inflammatory processes through inhibiting NF-κB activation. NF-κB can interact with other transcription factors, and these interactions thereby lead to greater transcriptional selectivity. Modification of transcription is likely to be a logical therapeutic target for acute lung injury.