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Molecular mechanisms of NF-B activation induced by bacterial lipopolysaccharide through Toll-like receptors

Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA

Sankar Ghosh

Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA, sankar.ghosh{at}yale.edu

Septic shock, caused by exaggerated host responses to various microbial products typified by lipopolysaccharide (LPS), remains the leading cause of death in trauma patients. Gaining insight into the nature of host interactions with LPS will certainly facilitate attempts to develop effective anti-sepsis drugs. Tremendous progress has been made during the past few years in understanding the mechanisms of pathogen-induced host responses. Toll-like receptor (TLR) 4 and 2 have been implicated as major receptors for signaling initiated by LPS and many other microbial products following their binding to CD14. In addition, many signaling intermediates involved in LPSinduced cell activation, particularly activation of the transcription factor NF-B, have been identified and characterized. Further investigations with these molecules will certainly reward us with more effective therapeutic drugs to treat septic shock as well as many other inflammatory and infectious disorders.

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