This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Held, T. K.
Right arrow Articles by Cross, A. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Held, T. K.
Right arrow Articles by Cross, A. S.

 Previous Article  |  Next Article 

Infection and Immunity, January 1999, p. 206-212, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Gamma Interferon Augments Macrophage Activation by Lipopolysaccharide by Two Distinct Mechanisms, at the Signal Transduction Level and via an Autocrine Mechanism Involving Tumor Necrosis Factor Alpha and Interleukin-1

Thomas K. Held,1,2 Xiao Weihua,3 Liang Yuan,2 Dhananjaya V. Kalvakolanu,3,4,5 and Alan S. Cross2,3,*

Abteilung für Innere Medizin m.S. Hämatologie und Onkologie, Virchow-Klinikum der Humboldt-Universität, 13357 Berlin, Germany,1 and Division of Infectious Diseases, Department of Medicine,2 Department of Microbiology & Immunology,4 Molecular and Cellular Biology Program,5 and Greenebaum Cancer Center, Program in Oncology,3 University of Maryland School of Medicine, Baltimore, Maryland 21201

Received 20 January 1998/Returned for modification 10 April 1998/Accepted 17 September 1998

When given in the presence of gamma interferon (IFN-gamma ), otherwise nontoxic doses of lipopolysaccharide (LPS or endotoxin) become highly lethal for mice. The mechanisms of this synergistic toxicity are not known. We considered the possibility that an interaction between the LPS-induced NF-kappa B and IFN-gamma -induced JAK-STAT pathways at the pretranscriptional level may enhance the LPS-induced signals. To test this hypothesis, we incubated murine macrophage RAW 264.7 cells with IFN-gamma for 2 h before addition of different doses of LPS. Consistent with the synergistic induction of inducible nitric oxide synthase mRNA and nitric oxide production by a combination of LPS and IFN-gamma , IFN-gamma strongly augmented LPS-induced NF-kappa B activation and accelerated the binding of NF-kappa B to DNA to as early as 5 min. In agreement with this, IFN-gamma pretreatment promoted rapid degradation of Ikappa B-alpha but not that of Ikappa B-beta . Inhibition of protein synthesis during IFN-gamma treatment suppressed LPS-initiated NF-kappa B binding. A rapidly induced protein appeared to be involved in IFN-gamma priming. Preincubation of cells with antibodies to tumor necrosis factor alpha or the interleukin-1 receptor partially reduced the priming effect of IFN-gamma . In a complementary manner, LPS enhanced the activation of signal-transducing activator of transcription 1 by IFN-gamma . These data suggest novel mechanisms for the synergy between IFN-gamma and LPS by which they cross-regulate the signal-transducing molecules. Through this mechanism, IFN-gamma may transform a given dose of LPS into a lethal stimulus capable of causing sepsis. It may also serve a beneficial purpose by enabling the host to respond quickly to relatively low doses of LPS and thereby activating antibacterial defenses.

* Corresponding author. Mailing address: Greenebaum Cancer Center, University of Maryland School of Medicine, 22 S. Greene St., Baltimore, MD 21201. Phone: (410) 328-2565. Fax: (410) 328-6896. E-mail: across{at}umcc01.umcc.ab.umd.edu.

Infection and Immunity, January 1999, p. 206-212, Vol. 67, No. 1
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Nijnik, A., Pistolic, J., Wyatt, A., Tam, S., Hancock, R. E. W. (2009). Human Cathelicidin Peptide LL-37 Modulates the Effects of IFN-{gamma} on APCs. J. Immunol. 183: 5788-5798 [Abstract] [Full Text]  
  • Tsai, C.-C., Kai, J.-I., Huang, W.-C., Wang, C.-Y., Wang, Y., Chen, C.-L., Fang, Y.-T., Lin, Y.-S., Anderson, R., Chen, S.-H., Tsao, C.-W., Lin, C.-F. (2009). Glycogen Synthase Kinase-3{beta} Facilitates IFN-{gamma}-Induced STAT1 Activation by Regulating Src Homology-2 Domain-Containing Phosphatase 2. J. Immunol. 183: 856-864 [Abstract] [Full Text]  
  • Zhu, X., Chang, M. S., Hsueh, R. C., Taussig, R., Smith, K. D., Simon, M. I., Choi, S. (2006). Dual Ligand Stimulation of RAW 264.7 Cells Uncovers Feedback Mechanisms That Regulate TLR-Mediated Gene Expression. J. Immunol. 177: 4299-4310 [Abstract] [Full Text]  
  • Totemeyer, S., Sheppard, M., Lloyd, A., Roper, D., Dowson, C., Underhill, D., Murray, P., Maskell, D., Bryant, C. (2006). IFN-{gamma} Enhances Production of Nitric Oxide from Macrophages via a Mechanism That Depends on Nucleotide Oligomerization Domain-2.. J. Immunol. 176: 4804-4810 [Abstract] [Full Text]  
  • Matsue, H., Yao, J., Matsue, K., Nagasaka, A., Sugiyama, H., Aoki, R., Kitamura, M., Shimada, S. (2006). Gap Junction-Mediated Intercellular Communication between Dendritic Cells (DCs) Is Required for Effective Activation of DCs. J. Immunol. 176: 181-190 [Abstract] [Full Text]  
  • Buhtoiarov, I. N., Lum, H. D., Berke, G., Sondel, P. M., Rakhmilevich, A. L. (2006). Synergistic Activation of Macrophages via CD40 and TLR9 Results in T Cell Independent Antitumor Effects. J. Immunol. 176: 309-318 [Abstract] [Full Text]  
  • Gordon, M. A., Jack, D. L., Dockrell, D. H., Lee, M. E., Read, R. C. (2005). Gamma Interferon Enhances Internalization and Early Nonoxidative Killing of Salmonella enterica Serovar Typhimurium by Human Macrophages and Modifies Cytokine Responses. Infect. Immun. 73: 3445-3452 [Abstract] [Full Text]  
  • Schroder, K., Hertzog, P. J., Ravasi, T., Hume, D. A. (2004). Interferon-{gamma}: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75: 163-189 [Abstract] [Full Text]  
  • Jaramillo, M., Gowda, D. C., Radzioch, D., Olivier, M. (2003). Hemozoin Increases IFN-{gamma}-Inducible Macrophage Nitric Oxide Generation Through Extracellular Signal-Regulated Kinase- and NF-{kappa}B-Dependent Pathways. J. Immunol. 171: 4243-4253 [Abstract] [Full Text]  
  • Foster, N., Hulme, S. D., Barrow, P. A. (2003). Induction of Antimicrobial Pathways during Early-Phase Immune Response to Salmonella spp. in Murine Macrophages: Gamma Interferon (IFN-{gamma}) and Upregulation of IFN-{gamma} Receptor Alpha Expression Are Required for NADPH Phagocytic Oxidase gp91-Stimulated Oxidative Burst and Control of Virulent Salmonella spp.. Infect. Immun. 71: 4733-4741 [Abstract] [Full Text]  
  • Augusto, L. A., Synguelakis, M., Espinassous, Q., Lepoivre, M., Johansson, J., Chaby, R. (2003). Cellular Antiendotoxin Activities of Lung Surfactant Protein C in Lipid Vesicles. Am. J. Respir. Crit. Care Med. 168: 335-341 [Abstract] [Full Text]  
  • Christopherson, J. A., Munson, E. L., England, D. M., Croke, C. L., Remington, M. C., Molitor, M. L., DeCoster, D. J., Callister, S. M., Schell, R. F. (2003). Destructive Arthritis in Vaccinated Interferon Gamma-Deficient Mice Challenged with Borrelia burgdorferi: Modulation by Tumor Necrosis Factor Alpha. CVI 10: 44-52 [Abstract] [Full Text]  
  • Baranova, I., Vishnyakova, T., Bocharov, A., Chen, Z., Remaley, A. T., Stonik, J., Eggerman, T. L., Patterson, A. P. (2002). Lipopolysaccharide Down Regulates Both Scavenger Receptor B1 and ATP Binding Cassette Transporter A1 in RAW Cells. Infect. Immun. 70: 2995-3003 [Abstract] [Full Text]  
  • Khan, A. Q., Shen, Y., Wu, Z.-Q., Wynn, T. A., Snapper, C. M. (2002). Endogenous Pro- and Anti-Inflammatory Cytokines Differentially Regulate an In Vivo Humoral Response to Streptococcus pneumoniae. Infect. Immun. 70: 749-761 [Abstract] [Full Text]  
  • Lemmink, H. H., Tuyt, L., Knol, G., Krikke, E., Vellenga, E. (2001). Identification of LIL-STAT in monocytic leukemia cells and monocytes after stimulation with interleukin-6 or interferon gamma. Blood 98: 3849-3852 [Abstract] [Full Text]  
  • Piaggio, E., Sanceau, J., Revelli, S., Bottasso, O., Wietzerbin, J., Serra, E. (2001). Trypanocidal Drug Benznidazole Impairs Lipopolysaccharide Induction of Macrophage Nitric Oxide Synthase Gene Transcription Through Inhibition of NF-{kappa}B Activation. J. Immunol. 167: 3422-3426 [Abstract] [Full Text]  
  • Quiding-Jarbrink, M., Smith, D. A., Bancroft, G. J. (2001). Production of Matrix Metalloproteinases in Response to Mycobacterial Infection. Infect. Immun. 69: 5661-5670 [Abstract] [Full Text]  
  • Barouch, R., Kazimirsky, G., Appel, E., Brodie, C. (2001). Nerve growth factor regulates TNF-{alpha} production in mouse macrophages via MAP kinase activation. J. Leukoc. Biol. 69: 1019-1026 [Abstract] [Full Text]  
  • Lee, J. Y., Sullivan, K. E. (2001). Gamma Interferon and Lipopolysaccharide Interact at the Level of Transcription To Induce Tumor Necrosis Factor Alpha Expression. Infect. Immun. 69: 2847-2852 [Abstract] [Full Text]  
  • Doughty, L. A., Nguyen, K. B., Durbin, J. E., Biron, C. A. (2001). A Role for IFN-{{alpha}}{{beta}} in Virus Infection-Induced Sensitization to Endotoxin. J. Immunol. 166: 2658-2664 [Abstract] [Full Text]  
  • Faure, E., Thomas, L., Xu, H., Medvedev, A. E., Equils, O., Arditi, M. (2001). Bacterial Lipopolysaccharide and IFN-{{gamma}} Induce Toll-Like Receptor 2 and Toll-Like Receptor 4 Expression in Human Endothelial Cells: Role of NF-{{kappa}}B Activation. J. Immunol. 166: 2018-2024 [Abstract] [Full Text]  
  • Cramer, L. A., Nelson, S. L., Klemsz, M. J. (2000). Synergistic Induction of the Tap-1 Gene by IFN-{gamma} and Lipopolysaccharide in Macrophages Is Regulated by STAT1. J. Immunol. 165: 3190-3197 [Abstract] [Full Text]  
  • Rosenberger, C. M., Scott, M. G., Gold, M. R., Hancock, R. E. W., Finlay, B. B. (2000). Salmonella typhimurium Infection and Lipopolysaccharide Stimulation Induce Similar Changes in Macrophage Gene Expression. J. Immunol. 164: 5894-5904 [Abstract] [Full Text]  
  • McGuirk, P., Mills, K. H. G. (2000). A Regulatory Role for Interleukin 4 in Differential Inflammatory Responses in the Lung following Infection of Mice Primed with Th1- or Th2-Inducing Pertussis Vaccines. Infect. Immun. 68: 1383-1390 [Abstract] [Full Text]  
  • Cario, E., Rosenberg, I. M., Brandwein, S. L., Beck, P. L., Reinecker, H.-C., Podolsky, D. K. (2000). Lipopolysaccharide Activates Distinct Signaling Pathways in Intestinal Epithelial Cell Lines Expressing Toll-Like Receptors. J. Immunol. 164: 966-972 [Abstract] [Full Text]  
  • Salkowski, C. A., Kopydlowski, K., Blanco, J., Cody, M. J., McNally, R., Vogel, S. N. (1999). IL-12 Is Dysregulated in Macrophages from IRF-1 and IRF-2 Knockout Mice. J. Immunol. 163: 1529-1536 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»