PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of iaiPermissionsJournals.ASM.orgJournalIAI ArticleJournal InfoAuthorsReviewers
 
Infect Immun. 1995 April; 63(4): 1529–1534.
PMCID: PMC173185

Lipopolysaccharide-inducible and salicylate-sensitive nuclear factor(s) on human tumor necrosis factor alpha promoter.

Abstract

Lipopolysaccharide (LPS) is one of the most potent trigger substances for monocytes and macrophages causing secretion of tumor necrosis factor alpha (TNF-alpha) and other inflammatory mediators. The nature of the nuclear factors involved in human TNF-alpha gene regulation is still unknown. Nuclear factor kappa B (NF-kappa B) proteins have been suggested to play an important role in gene transcription of inflammatory mediators when monocytes are stimulated with LPS. However, it remains unclear whether these nuclear factors are the only ones involved in human TNF-alpha gene regulation. In this report, to further the identification of nuclear factor(s) involved in TNF-alpha gene regulation, human monocytic THP-1 cells were transfected with a series of truncated versions of human TNF-alpha promoter. A 98-bp region located from nucleotides -584 to -487 demonstrated strong promoter activity. Electrophoretic mobility shift assays demonstrated that a 64-bp fragment located within the 98-bp region and lacking any potential NF-kappa B-binding sites avidly bound LPS-challenged THP-1 nuclear protein. Although this binding was inhibited in salicylate-treated cells, as was binding of NF-kappa B, the pattern of binding was found to differ from that noted for NF-kappa B. Analysis of this 64-bp fragment disclosed the absence of an NF-kappa B consensus sequence, suggesting a novel nuclear DNA-binding protein necessary for the initiation of human TNF-alpha transcription other than, or in addition to, NF-kappa B.

Full Text

The Full Text of this article is available as a PDF (293K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Baeuerle PA. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits. Biochim Biophys Acta. 1991 Apr 16;1072(1):63–80. [PubMed]
  • Beutler B, Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. [PubMed]
  • Beutler B, Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. [PubMed]
  • Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. [PubMed]
  • Bevilacqua MP, Stengelin S, Gimbrone MA, Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. [PubMed]
  • Collart MA, Baeuerle P, Vassalli P. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Mol Cell Biol. 1990 Apr;10(4):1498–1506. [PMC free article] [PubMed]
  • Collart MA, Belin D, Vassalli JD, de Kossodo S, Vassalli P. Gamma interferon enhances macrophage transcription of the tumor necrosis factor/cachectin, interleukin 1, and urokinase genes, which are controlled by short-lived repressors. J Exp Med. 1986 Dec 1;164(6):2113–2118. [PMC free article] [PubMed]
  • Cordle SR, Donald R, Read MA, Hawiger J. Lipopolysaccharide induces phosphorylation of MAD3 and activation of c-Rel and related NF-kappa B proteins in human monocytic THP-1 cells. J Biol Chem. 1993 Jun 5;268(16):11803–11810. [PubMed]
  • Dixit VM, Green S, Sarma V, Holzman LB, Wolf FW, O'Rourke K, Ward PA, Prochownik EV, Marks RM. Tumor necrosis factor-alpha induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J Biol Chem. 1990 Feb 15;265(5):2973–2978. [PubMed]
  • Drouet C, Shakhov AN, Jongeneel CV. Enhancers and transcription factors controlling the inducibility of the tumor necrosis factor-alpha promoter in primary macrophages. J Immunol. 1991 Sep 1;147(5):1694–1700. [PubMed]
  • Faisst S, Meyer S. Compilation of vertebrate-encoded transcription factors. Nucleic Acids Res. 1992 Jan 11;20(1):3–26. [PMC free article] [PubMed]
  • Forehand JR, Pabst MJ, Phillips WA, Johnston RB., Jr Lipopolysaccharide priming of human neutrophils for an enhanced respiratory burst. Role of intracellular free calcium. J Clin Invest. 1989 Jan;83(1):74–83. [PMC free article] [PubMed]
  • Gifford GE, Lohmann-Matthes ML. Requirement for the continual presence of lipopolysaccharide for production of tumor necrosis factor by thioglycollate-induced peritoneal murine macrophages. Int J Cancer. 1986 Jul 15;38(1):135–137. [PubMed]
  • Goldfeld AE, Doyle C, Maniatis T. Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9769–9773. [PubMed]
  • Kopp E, Ghosh S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science. 1994 Aug 12;265(5174):956–959. [PubMed]
  • Kunkel SL, Spengler M, May MA, Spengler R, Larrick J, Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380–5384. [PubMed]
  • Mahé Y, Mukaida N, Kuno K, Akiyama M, Ikeda N, Matsushima K, Murakami S. Hepatitis B virus X protein transactivates human interleukin-8 gene through acting on nuclear factor kB and CCAAT/enhancer-binding protein-like cis-elements. J Biol Chem. 1991 Jul 25;266(21):13759–13763. [PubMed]
  • Matsusaka T, Fujikawa K, Nishio Y, Mukaida N, Matsushima K, Kishimoto T, Akira S. Transcription factors NF-IL6 and NF-kappa B synergistically activate transcription of the inflammatory cytokines, interleukin 6 and interleukin 8. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10193–10197. [PubMed]
  • Müller JM, Ziegler-Heitbrock HW, Baeuerle PA. Nuclear factor kappa B, a mediator of lipopolysaccharide effects. Immunobiology. 1993 Apr;187(3-5):233–256. [PubMed]
  • Nathan CF. Secretory products of macrophages. J Clin Invest. 1987 Feb;79(2):319–326. [PMC free article] [PubMed]
  • Nedospasov SA, Shakhov AN, Turetskaya RL, Mett VA, Azizov MM, Georgiev GP, Korobko VG, Dobrynin VN, Filippov SA, Bystrov NS, et al. Tandem arrangement of genes coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta) in the human genome. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):611–624. [PubMed]
  • Nedwin GE, Naylor SL, Sakaguchi AY, Smith D, Jarrett-Nedwin J, Pennica D, Goeddel DV, Gray PW. Human lymphotoxin and tumor necrosis factor genes: structure, homology and chromosomal localization. Nucleic Acids Res. 1985 Sep 11;13(17):6361–6373. [PMC free article] [PubMed]
  • Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell. 1989 Dec 22;59(6):1203–1211. [PubMed]
  • Pober JS, Gimbrone MA, Jr, Lapierre LA, Mendrick DL, Fiers W, Rothlein R, Springer TA. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol. 1986 Sep 15;137(6):1893–1896. [PubMed]
  • Poli V, Balena R, Fattori E, Markatos A, Yamamoto M, Tanaka H, Ciliberto G, Rodan GA, Costantini F. Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO J. 1994 Mar 1;13(5):1189–1196. [PubMed]
  • Raetz CR. Biochemistry of endotoxins. Annu Rev Biochem. 1990;59:129–170. [PubMed]
  • Schleif R. DNA binding by proteins. Science. 1988 Sep 2;241(4870):1182–1187. [PubMed]
  • Schreiber E, Matthias P, Müller MM, Schaffner W. Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989 Aug 11;17(15):6419–6419. [PMC free article] [PubMed]
  • Shakhov AN, Collart MA, Vassalli P, Nedospasov SA, Jongeneel CV. Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J Exp Med. 1990 Jan 1;171(1):35–47. [PMC free article] [PubMed]
  • Shapira L, Takashiba S, Amar S, Van Dyke TE. Porphyromonas gingivalis lipopolysaccharide stimulation of human monocytes: dependence on serum and CD14 receptor. Oral Microbiol Immunol. 1994 Apr;9(2):112–117. [PubMed]
  • Shapira L, Takashiba S, Champagne C, Amar S, Van Dyke TE. Involvement of protein kinase C and protein tyrosine kinase in lipopolysaccharide-induced TNF-alpha and IL-1 beta production by human monocytes. J Immunol. 1994 Aug 15;153(4):1818–1824. [PubMed]
  • Stein B, Baldwin AS., Jr Distinct mechanisms for regulation of the interleukin-8 gene involve synergism and cooperativity between C/EBP and NF-kappa B. Mol Cell Biol. 1993 Nov;13(11):7191–7198. [PMC free article] [PubMed]
  • Strieter RM, Kunkel SL, Showell HJ, Remick DG, Phan SH, Ward PA, Marks RM. Endothelial cell gene expression of a neutrophil chemotactic factor by TNF-alpha, LPS, and IL-1 beta. Science. 1989 Mar 17;243(4897):1467–1469. [PubMed]
  • Takashiba S, Shapira L, Amar S, Van Dyke TE. Cloning and characterization of human TNF alpha promoter region. Gene. 1993 Sep 15;131(2):307–308. [PubMed]
  • Takashiba S, Takigawa M, Takahashi K, Myokai F, Nishimura F, Chihara T, Kurihara H, Nomura Y, Murayama Y. Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha. Infect Immun. 1992 Dec;60(12):5253–5258. [PMC free article] [PubMed]
  • Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A, et al. Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med. 1988 Mar 1;167(3):1211–1227. [PMC free article] [PubMed]
  • Tsuchiya S, Kobayashi Y, Goto Y, Okumura H, Nakae S, Konno T, Tada K. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982 Apr;42(4):1530–1536. [PubMed]
  • Vincenti MP, Burrell TA, Taffet SM. Regulation of NF-kappa B activity in murine macrophages: effect of bacterial lipopolysaccharide and phorbol ester. J Cell Physiol. 1992 Jan;150(1):204–213. [PubMed]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)