Transcriptional mechanisms of acute lung injury

Acute lung injury occurs as a result of a cascade of cellular events initia ted 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 mechani sms. Nuclear factor-kappaB (NF-kappaB) is one critical transcription factor required for maximal expression of many cytokines involved in the pathogen esis of acute lung injury. Activation and regulation of NF-kappaB are tight ly controlled by a complicated signaling cascade. In acute lung injury caus ed by infection of bacteria, Toll-like receptors play a central role in ini tiating the innate immune system and activating NF-kappaB. Anti-inflammator y cytokines such as interleukin-10 and interleukin-13 have been shown to su ppress inflammatory processes through inhibiting NF-kappaB activation. NF-k appaB can interact with other transcription factors, and these interactions thereby lead to greater transcriptional selectivity. Modification of trans cription is likely to be a logical therapeutic target for acute lung injury .