Elsevier

Immunobiology

Volume 187, Issues 3–5, April 1993, Pages 233-256
Immunobiology

Nuclear factor kappa B, a mediator of lipopolysaccharide effects

https://doi.org/10.1016/S0171-2985(11)80342-6Get rights and content

Abstract

Exposure of certain cell types to bacterial lipopolysaccharide (LPS) leads to activation of nuclear factor kappa B (NF-ϰB), an inducible transcription factor. One of NF-ϰB's unique properties is its posttranslational activation via release of an inhibitory subunit, called inhibitor of NF-ϰB (IϰB), from a sequestered cytoplasmic form. This event is also triggered under various other conditions of biomedical importance. Other bacterial toxins, tumor necrosis factor-α (TNF), interleukin-1 (IL-1), T cell mitogens, UV light, γ rays and oxidative stress were reported to induce NF-ϰB. The activated form of NF-ϰB, which is rapidly taken up into nuclei, initiates transcription from immediate early genes in a wide variety of cell types. Most of the target genes for NF-ϰB are of relevance for the immune response and can be grouped into those encoding cytokines, cell surface receptors, acute phase proteins and viral genomes, such as that of human immunodeficiency virus type 1 (HIV-1). We will discuss recent experimental evidences suggesting that LPS might share a pathway of NF-ϰB activation with other inducers of the factor. This common pathway may involve reactive oxygen intermediates (ROI) as messenger molecules.

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      LPS causes peripheral inflammation through activation of toll-like receptor 4 (TLR4) and recruitment of adaptor proteins (MyD88, TIRAP, TRIF, TRAM, and SARM) (Kawai et al., 2001; O’Neill and Bowie, 2007). This activation causes translocation of transcription factor NF-κB to the nucleus (Cordle et al., 1993; Müller et al., 1993), increasing cytokine gene and protein expression (Cho et al., 2003). Increased peripheral cytokines can directly cross the blood-brain barrier through active transport (Banks et al., 1989, 1991; Banks et al., 1994; Pan and Kastin, 2002) and activate vagal afferents (Balan et al., 2011; Buller, 2001) to induce neuroinflammation through a process involving activation of microglia (Henry et al., 2009; Sweitzer et al., 1999) and astrocytes (Sweitzer et al., 1999).

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    Dr. Patrick A. Baeuerle, Laboratory for Molecular Biology, Gene Center, Am Klopferspitz 18a, 8033 Martinsried, Germany

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