Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B.

Abstract

Tumor necrosis factor a and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor cB ( ABSTRACTBinding of peptide hormones to surface membrane receptors leads to the transcription of specific genes within relevant target cells. How these signals are transduced to alter gene expression is largely unknown, but this mechanism probably involves a sequence of enzymatic steps that activate factors in the nucleus that modulate transcription. We now demonstrate that two different peptide hormones, or cytokines, stimulate the human immunodeficiency virus enhancer, and this effect is mediated by nuclear factor (NF) KB (nuclear factor that binds the K immunoglobulin light chain gene enhancer). These cytokines, tumor necrosis factor a and interleukin 1, act on multiple cell types and represent the only naturally occurring activators of this transcription factor among eight cytokines examined. Although NF-KB binding can be stimulated by phorbol 12-myristate 13-acetate, tumor necrosis factor a acts through an independent mechanism, inducing NF-KB binding in HT-2 cells, which did not show increased binding in'response to phorbol 12-myristate 13-acetate, and causing superinduction in Jurkat T-lymphoma cells. Tumor necrosis factor a is also a more selective activator of T cells than phorbol 12-myristate 13-acetate, having no effect on lymphokine production in EL-4 cells at the same time it induces NF-KB. These findings suggest that human immunodeficiency virus gene expression can be induced in T cells without activating lymphokine secretion and that the role of these cytokines in the activation of latent human immunodeficiency virus infection deserves further clinical evaluation. Finally, this link between binding at the surface membrane and stimulation of a specific transcription factor should help derme intermediates for these cytokine activation pathways.

Upregulation of cyclooxygenase-2 is accompanied by increased expression of nuclear factor-κB and IκB kinase-α in human colorectal cancer epithelial cells

“…(3) More recently, NF-kB constitutive activity, as observed in Hodgkin's lymphoma cells, has been associated with a mutation in the gene encoding the IkB-inhibitor (Krappmann et al, 1999), which can lead to impaired control of NF-kB activity and hence to enhanced nuclear activity (Bours et al, 2000). The NF-kB transcription factor is activated in response to a broad range of preapoptotic stimuli (Osborn et al, 1989;Brach et al, 1991;Schreck et al, 1991), dissociates from its attached inhibitory protein IkB and translocates to the nucleus to induce the expression of target genes, including several well-known antiapoptotic genes such as TNF-receptor-associated factor 1 (TRAF1), and TRAF2, cIAPs, manganese superoxide dismutase, A20 and IEX-IL (Wang et al, 1998;Wu et al, 1998). Although NF-kB has been previously shown to be expressed at high levels in human colonic adenomatous polyps, our investigations have demonstrated for the first time (to the best of our knowledge) that IKKa, cytoplasmic inactive NF-kB-p65 protein and putative active endonuclear NF-kB-p65 protein are significantly increased in malignant colorectal epithelial cells.…”

Ozone induction of cytokine‐induced neutrophil chemoattractant (CINC) and nuclear factor‐κb in rat lung: inhibition by corticosteroids

“…Since both TNF-~ and IL-1 can induce NF-IcB [27][28][29], it is tempting to postulate that ozone may induce TNF-c~ and IL-1 which in turn increase NF-xB-binding to cause CINC mRNA upregulation. As ozone is a powerful oxidising agent, it is also possible that it can induce an increase in NF-xB-binding directly since hydrogen peroxide and other oxidants have been shown to activate rapidly NF-xB in certain cell lines in vitro [30,31].…”

CD40 expression on human pancreatic duct cells: role in nuclear factor-kappa B activation and production of pro-inflammatory cytokines

“…Briefly, Capan-2 cells were incubated for 2 h under the different conditions tested: in medium alone, with untransfected fibroblasts, or with CD40L-transfected fibroblasts. Nuclear extracts were prepared as previously described [32]. The double-stranded consensus-binding sequences for the EMSA comprised the oligonucleotide 5′-AGTTGAGGGG-ACTTTCCCAGG-3′ for NF-κB and for the mutant NF-κB, created with a G→C substitution.…”