Transcriptional mechanisms of acute lung injury.
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-kappa B (NF-kappa B) 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-kappa B 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-kappa B. Anti-inflammatory cytokines such as interleukin-10 and interleukin-13 have been shown to suppress inflammatory processes through inhibiting NF-kappa B activation. NF-kappa B 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.
Fan
J
J
Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, USA. jiefan@uic.edu
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Malik
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D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D018407:Bacterial Physiological Phenomena; D029721:Drosophila Proteins; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D012128:Respiratory Distress Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051193:Toll-Like Receptors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D014157:Transcription Factors